CTSC — 516 ClinVar variants

All ClinVar germline CTSC variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 169 flagged for review →

60 Pathogenic · 9 Pathogenic/Likely pathogenic · 14 Likely pathogenic · 18 Conflicting · 43 Benign · 3 Benign/Likely benign · 189 Likely benign · 180 Uncertain significance

Full CTSC gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 169

Variants where the independent computational evidence doesn't line up with the clinical picture — a QC signal for a second look, not a reclassification.

Predictors vs ClinVar 5

ClinVar calls these pathogenic, but the computational predictors lean tolerated — the highest-value review flag.

CTSC p.Arg272His Pathogenic/Likely pathogenic Multiple submitters
periodontitis, aggressive
CTSC p.Arg339Cys Pathogenic/Likely pathogenic Multiple submitters
periodontitis, aggressive
CTSC p.Ala253Thr Pathogenic Single submitter
periodontitis, aggressive
CTSC p.Arg132Gly Likely pathogenic Single submitter
Papillon-Lefevre disease
CTSC p.Tyr168Cys Pathogenic Single submitter
Papillon-Lefevre disease

Predictors agree, ClinVar conflicts 8

ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.

CTSC p.Arg132Gln Conflicting Single submitter
periodontitis, aggressive
CTSC p.Arg210Gln Conflicting Single submitter
Papillon-Lefevre disease
CTSC p.Arg272Ser Conflicting Single submitter
periodontitis, aggressive
CTSC p.Gln286Arg Conflicting Single submitter
Papillon-Lefevre disease
CTSC p.Gly300Asp Conflicting Single submitter
Papillon-Lefevre disease
CTSC p.Ile306Thr Conflicting Single submitter
Inborn genetic diseases
CTSC p.Ser6Ala Conflicting Single submitter
periodontitis, aggressive
CTSC p.Tyr345His Conflicting Single submitter
periodontitis, aggressive

Predictors lean, ClinVar uncertain 83

ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.

CTSC p.Ala10Val Uncertain significance Multiple submitters
Papillon-Lefevre disease
CTSC p.Ala269Val Uncertain significance Multiple submitters
Inborn genetic diseases
CTSC p.Arg442His Uncertain significance Multiple submitters
Inborn genetic diseases
CTSC p.Cys118Phe Uncertain significance Multiple submitters
periodontitis, aggressive
CTSC p.Cys291Tyr Uncertain significance Multiple submitters
Haim-Munk syndrome
CTSC p.Glu401Lys Uncertain significance Multiple submitters
periodontitis, aggressive
CTSC p.Gly47Val Uncertain significance Multiple submitters
periodontitis, aggressive
CTSC p.His366Leu Uncertain significance Multiple submitters
Haim-Munk syndrome
CTSC p.Ile282Val Uncertain significance Multiple submitters
Inborn genetic diseases
CTSC p.Ile87Val Uncertain significance Multiple submitters
periodontitis, aggressive
CTSC p.Phe439Leu Uncertain significance Multiple submitters
Papillon-Lefevre disease
CTSC p.Ser209Arg Uncertain significance Multiple submitters
periodontitis, aggressive
CTSC p.Thr188Ala Uncertain significance Multiple submitters
Inborn genetic diseases
CTSC p.Tyr170Cys Uncertain significance Multiple submitters
Papillon-Lefevre disease
CTSC p.Val22Leu Uncertain significance Multiple submitters
Inborn genetic diseases
CTSC p.Ala145Gly Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Ala154Val Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Ala21Val Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Ala307Thr Uncertain significance Single submitter
Haim-Munk syndrome
CTSC p.Ala311Thr Uncertain significance Single submitter
Haim-Munk syndrome
CTSC p.Ala417Thr Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Ala417Val Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Ala449Ser Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Arg442Leu Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Asn119Ser Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Asn148Asp Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Asn356Ser Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Asn398Ser Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Asp236Tyr Uncertain significance Single submitter
CTSC p.Asp336Asn Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Asp446Ala Uncertain significance Single submitter
CTSC p.Cys118Tyr Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Cys291Ser Uncertain significance Single submitter
Haim-Munk syndrome
CTSC p.Cys298Tyr Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Cys337Tyr Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Glu161Asp Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Glu192Gln Uncertain significance Single submitter
Haim-Munk syndrome
CTSC p.Glu335Gln Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Glu451Gln Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Gly111Asp Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Gly143Arg Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Gly297Val Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Gly2Arg Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Gly308Glu Uncertain significance Single submitter
Haim-Munk syndrome
CTSC p.Gly368Glu Uncertain significance Single submitter
CTSC-related disorder
CTSC p.Gly432Ser Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Gly91Arg Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.His127Pro Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.His241Asp Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.His366Arg Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Ile306Val Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Leu267Pro Uncertain significance Single submitter
CTSC p.Leu283Pro Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Leu316Val Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Leu78Arg Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Lys113Arg Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Lys332Thr Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Met122Val Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Met191Thr Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Met264Leu Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Met264Val Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Met333Thr Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Phe104Leu Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Phe374Ser Uncertain significance Single submitter
Haim-Munk syndrome
CTSC p.Phe84Leu Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Phe92Ile Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Pro303Leu Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Pro330Ala Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Ser205Arg Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Ser260Pro Uncertain significance Single submitter
CTSC p.Ser284Asn Uncertain significance Single submitter
CTSC p.Ser284Gly Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Ser342Ala Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Ser45Phe Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Thr115Ala Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Thr115Ile Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Thr327Ser Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Trp39Cys Uncertain significance Single submitter
CTSC p.Tyr107Cys Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Tyr294Cys Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Tyr304His Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Val43Leu Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Val56Ile Uncertain significance Single submitter
Inborn genetic diseases

Predictors split 73

The independent predictors disagree with each other — read with care.

CTSC p.Arg442Cys Uncertain significance Multiple submitters
periodontitis, aggressive
CTSC p.Asn398Lys Uncertain significance Multiple submitters
Papillon-Lefevre disease
CTSC p.Gly430Asp Uncertain significance Multiple submitters
periodontitis, aggressive
CTSC p.His127Arg Uncertain significance Multiple submitters
CTSC p.Pro303Ser Uncertain significance Multiple submitters
periodontitis, aggressive
CTSC p.Ser184Pro Uncertain significance Multiple submitters
Papillon-Lefevre disease
CTSC p.Ser257Gly Uncertain significance Multiple submitters
periodontitis, aggressive
CTSC p.Tyr32Cys Uncertain significance Multiple submitters
Inborn genetic diseases
CTSC p.Val317Gly Uncertain significance Multiple submitters
periodontitis, aggressive
CTSC p.Ala103Val Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Ala449Thr Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Ala449Val Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Arg250Gln Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Arg272Gly Uncertain significance Single submitter
CTSC p.Arg339His Uncertain significance Single submitter
CTSC p.Arg440Gln Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Arg440Trp Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Asn277Ser Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Asn80Ser Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Asn97Ser Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Asp336Ala Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Cys24Tyr Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Glu120Lys Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Glu318Gly Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Glu318Lys Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Glu375Lys Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Glu435Lys Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Gly18Asp Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Gly206Ala Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Gly207Asp Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Gly419Arg Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.His382Arg Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.His389Tyr Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.His390Arg Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Ile387Phe Uncertain significance Single submitter
Haim-Munk syndrome
CTSC p.Ile387Thr Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Ile450Thr Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Leu15Phe Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Leu198Gln Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Leu231Phe Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Leu362Val Uncertain significance Single submitter
Haim-Munk syndrome
CTSC p.Leu408Met Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Leu409Val Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Leu7Phe Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Lys100Arg Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Lys106Arg Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Lys169Glu Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Lys361Thr Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Met266Val Uncertain significance Single submitter
Haim-Munk syndrome
CTSC p.Pro323Arg Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Pro323Ser Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Pro59Leu Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Pro59Thr Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Ser55Leu Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Ser81Tyr Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Thr115Pro Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Thr189Ile Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Thr197Ile Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Thr280Ile Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Thr327Pro Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Tyr150Cys Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Tyr32His Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Tyr352Cys Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Tyr88Cys Conflicting Single submitter
Papillon-Lefevre disease
CTSC p.Tyr99His Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Tyr99Phe Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Val114Leu Uncertain significance Single submitter
periodontitis, aggressive
CTSC p.Val129Glu Uncertain significance Single submitter
Haim-Munk syndrome
CTSC p.Val240Ala Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Val240Gly Uncertain significance Single submitter
Papillon-Lefevre disease
CTSC p.Val288Leu Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Val348Ile Uncertain significance Single submitter
Inborn genetic diseases
CTSC p.Val365Ala Uncertain significance Single submitter
Haim-Munk syndrome

All CTSC variants

Pathogenic 60

c.319-1G>A Multiple submitters periodontitis, aggressive
c.-55C>A Multiple submitters Papillon-Lefevre disease
p.Arg210Ter Multiple submitters CTSC-related disorder
p.Gly139Arg Multiple submitters periodontitis, aggressive
p.Leu381fs Multiple submitters periodontitis, aggressive
p.Tyr32Ter Multiple submitters periodontitis, aggressive
c.318+1G>A Single submitter Papillon-Lefevre disease
c.319-1G>T Single submitter Papillon-Lefevre disease
c.889+1G>A Single submitter periodontitis, aggressive
p.Ala253Thr Single submitter periodontitis, aggressive ⚠
p.Ala417fs Single submitter periodontitis, aggressive
p.Arg203Ter Single submitter periodontitis, aggressive
p.Asp236fs Single submitter periodontitis, aggressive
p.Cys136fs Single submitter periodontitis, aggressive
p.Cys30Ter Single submitter periodontitis, aggressive
p.Gln160Ter Single submitter periodontitis, aggressive
p.Gln225fs Single submitter periodontitis, aggressive
p.Gln252Ter Single submitter Papillon-Lefevre disease
p.Gln286fs Single submitter periodontitis, aggressive
p.Gln286Ter Single submitter Papillon-Lefevre disease
p.Gln293Ter Single submitter periodontitis, aggressive
p.Gln42fs Single submitter periodontitis, aggressive
p.Gln90Ter Single submitter Papillon-Lefevre disease
p.Glu110Ter Single submitter periodontitis, aggressive
p.Glu287_Val288delinsAspTrpAlaTer Single submitter Papillon-Lefevre disease
p.Glu401fs Single submitter periodontitis, aggressive
p.Gly139Ter Single submitter periodontitis, aggressive
p.Gly242fs Single submitter periodontitis, aggressive
p.Gly350fs Single submitter Papillon-Lefevre disease
p.His208fs Single submitter Papillon-Lefevre disease
p.His366fs Single submitter Haim-Munk syndrome
p.His382_Tyr383insTer Single submitter periodontitis, aggressive
p.Leu16fs Single submitter periodontitis, aggressive
p.Leu196fs Single submitter periodontitis, aggressive
p.Leu7fs Single submitter periodontitis, aggressive
p.Lys176Ter Single submitter Papillon-Lefevre disease
p.Lys216_Pro217delinsAsnTer Single submitter periodontitis, aggressive
p.Phe261fs Single submitter Papillon-Lefevre disease
p.Phe374fs Single submitter periodontitis, aggressive
p.Ser146fs Single submitter periodontitis, aggressive
p.Thr186fs Single submitter Papillon-Lefevre disease
p.Thr189fs Single submitter periodontitis, aggressive
p.Trp101Ter Single submitter periodontitis, aggressive
p.Trp134Ter Single submitter periodontitis, aggressive
p.Trp185Ter Single submitter periodontitis, aggressive
p.Trp237Ter Single submitter periodontitis, aggressive
p.Trp429Ter Single submitter periodontitis, aggressive
p.Tyr117Ter Single submitter periodontitis, aggressive
p.Tyr168Cys Single submitter Papillon-Lefevre disease ⚠
p.Tyr170Ter Single submitter periodontitis, aggressive
p.Tyr190Ter Single submitter Papillon-Lefevre disease
p.Tyr310Ter Single submitter periodontitis, aggressive
p.Tyr341Ter Single submitter periodontitis, aggressive
p.Tyr347Cys Single submitter Papillon-Lefevre disease
p.Tyr67Ter Single submitter periodontitis, aggressive
p.Val64fs Single submitter periodontitis, aggressive
c.890-1G>A No assertion criteria Papillon-Lefevre disease
p.Phe351_Tyr352insTer No assertion criteria Papillon-Lefevre disease
p.Trp429Cys No assertion criteria Papillon-Lefevre disease
p.Tyr412Cys No assertion criteria periodontitis, aggressive

Pathogenic/Likely pathogenic 9

p.Arg250Ter Multiple submitters periodontitis, aggressive
p.Arg272His Multiple submitters periodontitis, aggressive ⚠
p.Arg272Pro Multiple submitters periodontitis, aggressive
p.Arg339Cys Multiple submitters periodontitis, aggressive ⚠
p.Gln252Leu Multiple submitters periodontitis, aggressive 1
p.Gly301Ser Multiple submitters Papillon-Lefevre disease
p.Leu196Pro Multiple submitters periodontitis, aggressive
p.Leu68Arg Multiple submitters periodontitis, aggressive
p.Lys63_Val64insTer Multiple submitters periodontitis, aggressive

Likely pathogenic 14

c.757+1G>T Multiple submitters periodontitis, aggressive
p.Asn427Thr Multiple submitters Papillon-Lefevre disease
c.173-2A>C Single submitter periodontitis, aggressive
c.485+1G>A Single submitter periodontitis, aggressive
c.486-25_492del Single submitter periodontitis, aggressive
c.641+1G>A Single submitter periodontitis, aggressive
c.642-2A>G Single submitter periodontitis, aggressive
p.Arg132Gly Single submitter Papillon-Lefevre disease ⚠
p.Glu435Ter Single submitter
p.Glu447Ter Single submitter periodontitis, aggressive
p.Trp39Ser Single submitter Papillon-Lefevre disease
p.Tyr304Asn Single submitter periodontitis, aggressive
p.Val249Phe Single submitter Haim-Munk syndrome
p.Thr121dup No assertion criteria Papillon-Lefevre disease

Conflicting classifications of pathogenicity 18

c.319-15C>T Single submitter Papillon-Lefevre disease
c.642-15A>G Single submitter periodontitis, aggressive
p.Arg132Gln Single submitter periodontitis, aggressive ⚠
p.Arg210Gln Single submitter Papillon-Lefevre disease ⚠
p.Arg272Ser Single submitter periodontitis, aggressive ⚠
p.Gln286Arg Single submitter Papillon-Lefevre disease ⚠
p.Glu318= Single submitter Papillon-Lefevre disease
p.Gly300Asp Single submitter Papillon-Lefevre disease ⚠
p.Gly4= Single submitter periodontitis, aggressive
p.His346= Single submitter Haim-Munk syndrome
p.Ile243= Single submitter Haim-Munk syndrome
p.Ile306Thr Single submitter Inborn genetic diseases ⚠
p.Met1Val Single submitter Papillon-Lefevre disease
p.Pro27= Single submitter Haim-Munk syndrome
p.Ser6Ala Single submitter periodontitis, aggressive ⚠
p.Tyr345His Single submitter periodontitis, aggressive ⚠
p.Tyr438= Single submitter Papillon-Lefevre disease
p.Tyr88Cys Single submitter Papillon-Lefevre disease ⚠

Benign 43

c.172+106G>A Multiple submitters
c.173-79A>T Multiple submitters
c.173-7del Multiple submitters Haim-Munk syndrome
c.318+101A>T Multiple submitters
c.318+256G>A Multiple submitters
c.318+279C>A Multiple submitters
c.318+53C>A Multiple submitters
c.318+6700T>G Multiple submitters
c.318+8422C>T Multiple submitters
c.757+37T>C Multiple submitters
c.758-153A>G Multiple submitters
c.758-185A>G Multiple submitters
c.-18T>C Multiple submitters Haim-Munk syndrome
c.-62C>T Multiple submitters Papillon-Lefevre disease
c.-74T>C Multiple submitters Haim-Munk syndrome
p.Ile153= Multiple submitters periodontitis, aggressive
p.Ile153Thr Multiple submitters Haim-Munk syndrome
p.Thr275= Multiple submitters Haim-Munk syndrome
p.Thr391= Multiple submitters Papillon-Lefevre disease
c.173-19dup Single submitter Papillon-Lefevre disease
c.173-211A>G Single submitter
c.173-8_173-7del Single submitter periodontitis, aggressive
c.318+6449T>C Single submitter
c.318+8223A>G Single submitter
c.318+8224A>T Single submitter
c.318+8365T>A Single submitter
c.318+8366A>G Single submitter
c.318+8396_318+8397dup Single submitter
c.318+8396dup Single submitter
c.318+9dup Single submitter periodontitis, aggressive
c.319-18del Single submitter periodontitis, aggressive
c.319-96dup Single submitter
c.485+280T>G Single submitter
c.485+292A>C Single submitter
c.641+19dup Single submitter periodontitis, aggressive
c.642-198_642-195del Single submitter
c.757+177A>G Single submitter
c.757+186T>A Single submitter
c.757+9dup Single submitter periodontitis, aggressive
c.758-16T>A Single submitter Papillon-Lefevre disease
c.*253T>C Single submitter Haim-Munk syndrome
c.*279A>G Single submitter Papillon-Lefevre disease
c.318+8563G>A No assertion criteria CTSC-related disorder

Benign/Likely benign 3

p.His382= Multiple submitters Haim-Munk syndrome
p.Ile453Val Multiple submitters Haim-Munk syndrome
p.Thr431= Multiple submitters Papillon-Lefevre disease

Likely benign 189

c.-91T>G Multiple submitters Papillon-Lefevre disease
p.Thr189Ala Multiple submitters Papillon-Lefevre disease
c.172+10C>T Single submitter periodontitis, aggressive
c.172+11G>C Single submitter periodontitis, aggressive
c.172+13C>T Single submitter periodontitis, aggressive
c.172+15C>T Single submitter periodontitis, aggressive
c.172+19A>C Single submitter periodontitis, aggressive
c.172+8G>C Single submitter periodontitis, aggressive
c.172+8G>T Single submitter periodontitis, aggressive
c.173-10_173-7del Single submitter periodontitis, aggressive
c.173-11T>C Single submitter periodontitis, aggressive
c.173-15T>A Single submitter periodontitis, aggressive
c.173-15T>G Single submitter periodontitis, aggressive
c.173-19T>C Single submitter periodontitis, aggressive
c.173-6C>T Single submitter periodontitis, aggressive
c.173-7T>G Single submitter periodontitis, aggressive
c.173-8T>G Single submitter periodontitis, aggressive
c.318+13G>T Single submitter periodontitis, aggressive
c.318+17G>T Single submitter periodontitis, aggressive
c.318+20G>T Single submitter periodontitis, aggressive
c.318+9T>C Single submitter periodontitis, aggressive
c.319-10T>C Single submitter periodontitis, aggressive
c.319-11T>C Single submitter periodontitis, aggressive
c.319-17C>A Single submitter periodontitis, aggressive
c.319-17C>G Single submitter periodontitis, aggressive
c.319-17C>T Single submitter periodontitis, aggressive
c.319-19_319-13del Single submitter periodontitis, aggressive
c.319-20T>A Single submitter periodontitis, aggressive
c.319-4G>T Single submitter periodontitis, aggressive
c.319-5T>C Single submitter periodontitis, aggressive
c.485+11A>G Single submitter periodontitis, aggressive
c.485+12C>T Single submitter periodontitis, aggressive
c.486-14A>C Single submitter periodontitis, aggressive
c.486-17C>T Single submitter periodontitis, aggressive
c.486-20T>C Single submitter periodontitis, aggressive
c.486-9T>G Single submitter periodontitis, aggressive
c.641+10C>T Single submitter periodontitis, aggressive
c.641+12C>T Single submitter periodontitis, aggressive
c.641+20A>C Single submitter periodontitis, aggressive
c.641+20A>G Single submitter periodontitis, aggressive
c.641+8A>G Single submitter Haim-Munk syndrome
c.642-16T>C Single submitter periodontitis, aggressive
c.642-19A>G Single submitter periodontitis, aggressive
c.642-8C>G Single submitter periodontitis, aggressive
c.757+15C>T Single submitter periodontitis, aggressive
c.757+17A>G Single submitter periodontitis, aggressive
c.758-16dup Single submitter Papillon-Lefevre disease
c.758-16T>C Single submitter periodontitis, aggressive
c.758-17_758-16del Single submitter periodontitis, aggressive
c.758-17C>T Single submitter periodontitis, aggressive
c.758-19G>A Single submitter periodontitis, aggressive
c.758-19G>T Single submitter periodontitis, aggressive
c.758-20T>C Single submitter periodontitis, aggressive
c.758-20T>G Single submitter periodontitis, aggressive
c.758-5G>A Single submitter Papillon-Lefevre disease
c.758-5G>T Single submitter periodontitis, aggressive
c.758-6C>T Single submitter periodontitis, aggressive
c.889+13T>C Single submitter periodontitis, aggressive
c.889+18G>C Single submitter periodontitis, aggressive
c.889+19A>G Single submitter periodontitis, aggressive
c.889+9T>A Single submitter Papillon-Lefevre disease
c.889+9T>C Single submitter periodontitis, aggressive
c.890-11T>C Single submitter periodontitis, aggressive
c.890-13T>A Single submitter periodontitis, aggressive
c.890-18T>C Single submitter periodontitis, aggressive
c.890-20T>C Single submitter periodontitis, aggressive
c.890-5T>C Single submitter Papillon-Lefevre disease
c.890-6C>T Single submitter periodontitis, aggressive
p.Ala180= Single submitter periodontitis, aggressive
p.Ala21= Single submitter periodontitis, aggressive
p.Ala222= Single submitter periodontitis, aggressive
p.Ala269= Single submitter Papillon-Lefevre disease
p.Ala373= Single submitter periodontitis, aggressive
p.Ala74= Single submitter periodontitis, aggressive
p.Arg203= Single submitter periodontitis, aggressive
p.Arg250= Single submitter periodontitis, aggressive
p.Arg339= Single submitter periodontitis, aggressive
p.Arg440= Single submitter periodontitis, aggressive
p.Asn119= Single submitter Papillon-Lefevre disease
p.Asn165= Single submitter periodontitis, aggressive
p.Asn239= Single submitter periodontitis, aggressive
p.Asn29= Single submitter periodontitis, aggressive
p.Asn398= Single submitter periodontitis, aggressive
p.Asn80= Single submitter periodontitis, aggressive
p.Asp446= Single submitter periodontitis, aggressive
p.Cys136= Single submitter periodontitis, aggressive
p.Cys291= Single submitter periodontitis, aggressive
p.Cys30= Single submitter Haim-Munk syndrome
p.Cys337= Single submitter periodontitis, aggressive
p.Cys448= Single submitter periodontitis, aggressive
p.Cys54= Single submitter periodontitis, aggressive
p.Gln160= Single submitter periodontitis, aggressive
p.Gln182= Single submitter periodontitis, aggressive
p.Gln226= Single submitter periodontitis, aggressive
p.Gln312= Single submitter periodontitis, aggressive
p.Gln49= Single submitter periodontitis, aggressive
p.Gln60= Single submitter periodontitis, aggressive
p.Glu110= Single submitter periodontitis, aggressive
p.Glu268= Single submitter Haim-Munk syndrome
p.Glu299= Single submitter periodontitis, aggressive
p.Glu375= Single submitter periodontitis, aggressive
p.Glu447= Single submitter periodontitis, aggressive
p.Gly131= Single submitter periodontitis, aggressive
p.Gly20= Single submitter periodontitis, aggressive
p.Gly256= Single submitter Haim-Munk syndrome
p.Gly297= Single submitter periodontitis, aggressive
p.Gly300= Single submitter periodontitis, aggressive
p.Gly315= Single submitter periodontitis, aggressive
p.Gly326= Single submitter periodontitis, aggressive
p.Gly354= Single submitter periodontitis, aggressive
p.Gly368= Single submitter periodontitis, aggressive
p.Gly37= Single submitter periodontitis, aggressive
p.Gly386= Single submitter periodontitis, aggressive
p.Gly392= Single submitter Haim-Munk syndrome
p.Gly411= Single submitter periodontitis, aggressive
p.Gly413= Single submitter Papillon-Lefevre disease
p.Gly419= Single submitter Papillon-Lefevre disease
p.Gly58= Single submitter periodontitis, aggressive
p.Gly79= Single submitter periodontitis, aggressive
p.Gly91= Single submitter periodontitis, aggressive
p.His83= Single submitter periodontitis, aggressive
p.Ile212= Single submitter periodontitis, aggressive
p.Ile387= Single submitter periodontitis, aggressive
p.Ile424= Single submitter periodontitis, aggressive
p.Ile441= Single submitter periodontitis, aggressive
p.Leu14= Single submitter Papillon-Lefevre disease
p.Leu16= Single submitter periodontitis, aggressive
p.Leu167= Single submitter periodontitis, aggressive
p.Leu198= Single submitter periodontitis, aggressive
p.Leu316= Single submitter periodontitis, aggressive
p.Leu362= Single submitter periodontitis, aggressive
p.Leu393= Single submitter periodontitis, aggressive
p.Leu409= Single submitter periodontitis, aggressive
p.Leu7= Single submitter periodontitis, aggressive
p.Leu71= Single submitter periodontitis, aggressive
p.Leu78= Single submitter Papillon-Lefevre disease
p.Leu96= Single submitter periodontitis, aggressive
p.Lys169= Single submitter periodontitis, aggressive
p.Lys216= Single submitter periodontitis, aggressive
p.Lys309= Single submitter periodontitis, aggressive
p.Lys332= Single submitter periodontitis, aggressive
p.Lys63= Single submitter periodontitis, aggressive
p.Lys70= Single submitter periodontitis, aggressive
p.Phe174= Single submitter periodontitis, aggressive
p.Phe314= Single submitter periodontitis, aggressive
p.Phe351= Single submitter periodontitis, aggressive
p.Phe380= Single submitter periodontitis, aggressive
p.Pro213= Single submitter periodontitis, aggressive
p.Pro232= Single submitter periodontitis, aggressive
p.Pro323= Single submitter periodontitis, aggressive
p.Pro396= Single submitter periodontitis, aggressive
p.Pro399= Single submitter periodontitis, aggressive
p.Pro459= Single submitter periodontitis, aggressive
p.Pro5= Single submitter periodontitis, aggressive
p.Ser17= Single submitter periodontitis, aggressive
p.Ser184= Single submitter periodontitis, aggressive
p.Ser254= Single submitter periodontitis, aggressive
p.Ser263= Single submitter periodontitis, aggressive
p.Ser418= Single submitter Papillon-Lefevre disease
p.Ser428= Single submitter periodontitis, aggressive
p.Ser46= Single submitter periodontitis, aggressive
p.Ser48= Single submitter periodontitis, aggressive
p.Ser55= Single submitter periodontitis, aggressive
p.Ser81= Single submitter periodontitis, aggressive
p.Ter464= Single submitter periodontitis, aggressive
p.Thr121= Single submitter periodontitis, aggressive
p.Thr123= Single submitter periodontitis, aggressive
p.Thr138= Single submitter Papillon-Lefevre disease
p.Thr144= Single submitter periodontitis, aggressive
p.Thr189= Single submitter periodontitis, aggressive
p.Thr197= Single submitter periodontitis, aggressive
p.Thr325= Single submitter Papillon-Lefevre disease
p.Thr327= Single submitter periodontitis, aggressive
p.Thr414= Single submitter periodontitis, aggressive
p.Thr445= Single submitter periodontitis, aggressive
p.Thr85= Single submitter periodontitis, aggressive
p.Tyr117= Single submitter periodontitis, aggressive
p.Tyr150= Single submitter periodontitis, aggressive
p.Tyr259= Single submitter Haim-Munk syndrome
p.Tyr294= Single submitter periodontitis, aggressive
p.Tyr310= Single submitter Haim-Munk syndrome
p.Tyr340= Single submitter periodontitis, aggressive
p.Tyr383= Single submitter periodontitis, aggressive
p.Tyr67His Single submitter Inborn genetic diseases
p.Val129= Single submitter periodontitis, aggressive
p.Val56= Single submitter periodontitis, aggressive
p.Val65= Single submitter periodontitis, aggressive
c.318+6733C>T No assertion criteria CTSC-related disorder
c.-63C>A No assertion criteria CTSC-related disorder

Uncertain significance 180

p.Ala10Val Multiple submitters Papillon-Lefevre disease ⚠
p.Ala269Val Multiple submitters Inborn genetic diseases ⚠
p.Ala449fs Multiple submitters Haim-Munk syndrome
p.Arg442Cys Multiple submitters periodontitis, aggressive ⚠
p.Arg442His Multiple submitters Inborn genetic diseases ⚠
p.Asn398Lys Multiple submitters Papillon-Lefevre disease ⚠
p.Cys118Phe Multiple submitters periodontitis, aggressive ⚠
p.Cys291Tyr Multiple submitters Haim-Munk syndrome ⚠
p.Glu401Lys Multiple submitters periodontitis, aggressive ⚠
p.Gly430Asp Multiple submitters periodontitis, aggressive ⚠
p.Gly47Val Multiple submitters periodontitis, aggressive ⚠
p.His127Arg Multiple submitters ⚠
p.His366Leu Multiple submitters Haim-Munk syndrome ⚠
p.Ile282Val Multiple submitters Inborn genetic diseases ⚠
p.Ile87Val Multiple submitters periodontitis, aggressive ⚠
p.Phe439Leu Multiple submitters Papillon-Lefevre disease ⚠
p.Pro303Ser Multiple submitters periodontitis, aggressive ⚠
p.Ser184Pro Multiple submitters Papillon-Lefevre disease ⚠
p.Ser209Arg Multiple submitters periodontitis, aggressive ⚠
p.Ser257Gly Multiple submitters periodontitis, aggressive ⚠
p.Thr188Ala Multiple submitters Inborn genetic diseases ⚠
p.Tyr170Cys Multiple submitters Papillon-Lefevre disease ⚠
p.Tyr32Cys Multiple submitters Inborn genetic diseases ⚠
p.Val22Leu Multiple submitters Inborn genetic diseases ⚠
p.Val317Gly Multiple submitters periodontitis, aggressive ⚠
c.318+4_318+7del Single submitter Haim-Munk syndrome
c.318+4A>G Single submitter Haim-Munk syndrome
c.318+6787_318+6788del Single submitter Papillon-Lefevre disease
c.318+8487C>G Single submitter
c.319-3C>T Single submitter
c.319-4_319-3delinsAA Single submitter periodontitis, aggressive
c.641+3A>G Single submitter periodontitis, aggressive
c.757+3A>G Single submitter periodontitis, aggressive
c.757+5A>G Single submitter periodontitis, aggressive
c.757+6A>T Single submitter Papillon-Lefevre disease
c.758-16T>G Single submitter periodontitis, aggressive
c.758-7T>A Single submitter Papillon-Lefevre disease
c.-48G>A Single submitter Papillon-Lefevre disease
c.-49C>T Single submitter Haim-Munk syndrome
c.-55C>T Single submitter Papillon-Lefevre disease
c.-80G>C Single submitter Papillon-Lefevre disease
c.*350A>G Single submitter Haim-Munk syndrome
c.*381A>G Single submitter Haim-Munk syndrome
c.*414A>G Single submitter Haim-Munk syndrome
p.Ala103Val Single submitter periodontitis, aggressive ⚠
p.Ala145Gly Single submitter periodontitis, aggressive ⚠
p.Ala154Val Single submitter Inborn genetic diseases ⚠
p.Ala21Val Single submitter periodontitis, aggressive ⚠
p.Ala222del Single submitter Papillon-Lefevre disease
p.Ala307= Single submitter periodontitis, aggressive
p.Ala307Thr Single submitter Haim-Munk syndrome ⚠
p.Ala311Thr Single submitter Haim-Munk syndrome ⚠
p.Ala417Thr Single submitter Inborn genetic diseases ⚠
p.Ala417Val Single submitter Inborn genetic diseases ⚠
p.Ala449Ser Single submitter Inborn genetic diseases ⚠
p.Ala449Thr Single submitter periodontitis, aggressive ⚠
p.Ala449Val Single submitter periodontitis, aggressive ⚠
p.Arg250Gln Single submitter Inborn genetic diseases ⚠
p.Arg272Gly Single submitter ⚠
p.Arg339His Single submitter ⚠
p.Arg440Gln Single submitter periodontitis, aggressive ⚠
p.Arg440Trp Single submitter Papillon-Lefevre disease ⚠
p.Arg442Leu Single submitter Inborn genetic diseases ⚠
p.Asn119Ser Single submitter Inborn genetic diseases ⚠
p.Asn148Asp Single submitter Inborn genetic diseases ⚠
p.Asn277Ser Single submitter periodontitis, aggressive ⚠
p.Asn356Ser Single submitter Papillon-Lefevre disease ⚠
p.Asn398Ser Single submitter periodontitis, aggressive ⚠
p.Asn80Ser Single submitter periodontitis, aggressive ⚠
p.Asn97Ser Single submitter periodontitis, aggressive ⚠
p.Asp236Tyr Single submitter ⚠
p.Asp336Ala Single submitter periodontitis, aggressive ⚠
p.Asp336Asn Single submitter Papillon-Lefevre disease ⚠
p.Asp446Ala Single submitter ⚠
p.Asp446del Single submitter periodontitis, aggressive
p.Cys118Tyr Single submitter Papillon-Lefevre disease ⚠
p.Cys24Tyr Single submitter periodontitis, aggressive ⚠
p.Cys291Ser Single submitter Haim-Munk syndrome ⚠
p.Cys298Tyr Single submitter periodontitis, aggressive ⚠
p.Cys337Tyr Single submitter periodontitis, aggressive ⚠
p.Glu120Lys Single submitter periodontitis, aggressive ⚠
p.Glu161Asp Single submitter Inborn genetic diseases ⚠
p.Glu192Gln Single submitter Haim-Munk syndrome ⚠
p.Glu318Gly Single submitter periodontitis, aggressive ⚠
p.Glu318Lys Single submitter periodontitis, aggressive ⚠
p.Glu335Gln Single submitter Inborn genetic diseases ⚠
p.Glu375Lys Single submitter Papillon-Lefevre disease ⚠
p.Glu435Lys Single submitter periodontitis, aggressive ⚠
p.Glu451Gln Single submitter periodontitis, aggressive ⚠
p.Gly111Asp Single submitter Inborn genetic diseases ⚠
p.Gly143Arg Single submitter periodontitis, aggressive ⚠
p.Gly18Asp Single submitter Papillon-Lefevre disease ⚠
p.Gly206Ala Single submitter Inborn genetic diseases ⚠
p.Gly207Asp Single submitter Inborn genetic diseases ⚠
p.Gly297Val Single submitter periodontitis, aggressive ⚠
p.Gly2Arg Single submitter periodontitis, aggressive ⚠
p.Gly308Glu Single submitter Haim-Munk syndrome ⚠
p.Gly368Glu Single submitter CTSC-related disorder ⚠
p.Gly419Arg Single submitter Inborn genetic diseases ⚠
p.Gly432Ser Single submitter periodontitis, aggressive ⚠
p.Gly91Arg Single submitter periodontitis, aggressive ⚠
p.His127Pro Single submitter Papillon-Lefevre disease ⚠
p.His241Asp Single submitter Inborn genetic diseases ⚠
p.His366Arg Single submitter Inborn genetic diseases ⚠
p.His382Arg Single submitter Papillon-Lefevre disease ⚠
p.His389Tyr Single submitter periodontitis, aggressive ⚠
p.His390Arg Single submitter periodontitis, aggressive ⚠
p.Ile306Val Single submitter Inborn genetic diseases ⚠
p.Ile387Phe Single submitter Haim-Munk syndrome ⚠
p.Ile387Thr Single submitter Papillon-Lefevre disease ⚠
p.Ile450Thr Single submitter Papillon-Lefevre disease ⚠
p.Leu15Phe Single submitter Papillon-Lefevre disease ⚠
p.Leu198Gln Single submitter periodontitis, aggressive ⚠
p.Leu231Phe Single submitter Papillon-Lefevre disease ⚠
p.Leu267Pro Single submitter ⚠
p.Leu283Pro Single submitter periodontitis, aggressive ⚠
p.Leu316Val Single submitter Papillon-Lefevre disease ⚠
p.Leu362Val Single submitter Haim-Munk syndrome ⚠
p.Leu408Met Single submitter periodontitis, aggressive ⚠
p.Leu409Val Single submitter periodontitis, aggressive ⚠
p.Leu78Arg Single submitter periodontitis, aggressive ⚠
p.Leu7Phe Single submitter Papillon-Lefevre disease ⚠
p.Lys100Arg Single submitter periodontitis, aggressive ⚠
p.Lys106Arg Single submitter Inborn genetic diseases ⚠
p.Lys113Arg Single submitter periodontitis, aggressive ⚠
p.Lys169Glu Single submitter periodontitis, aggressive ⚠
p.Lys332Thr Single submitter Inborn genetic diseases ⚠
p.Lys361Thr Single submitter periodontitis, aggressive ⚠
p.Met122Val Single submitter periodontitis, aggressive ⚠
p.Met191Thr Single submitter Inborn genetic diseases ⚠
p.Met264Leu Single submitter periodontitis, aggressive ⚠
p.Met264Val Single submitter periodontitis, aggressive ⚠
p.Met266Val Single submitter Haim-Munk syndrome ⚠
p.Met333Thr Single submitter periodontitis, aggressive ⚠
p.Phe104Leu Single submitter periodontitis, aggressive ⚠
p.Phe374Ser Single submitter Haim-Munk syndrome ⚠
p.Phe84Leu Single submitter Papillon-Lefevre disease ⚠
p.Phe92Ile Single submitter Inborn genetic diseases ⚠
p.Pro303Leu Single submitter periodontitis, aggressive ⚠
p.Pro323Arg Single submitter Inborn genetic diseases ⚠
p.Pro323Ser Single submitter periodontitis, aggressive ⚠
p.Pro330Ala Single submitter Inborn genetic diseases ⚠
p.Pro59Leu Single submitter periodontitis, aggressive ⚠
p.Pro59Thr Single submitter periodontitis, aggressive ⚠
p.Ser205Arg Single submitter Papillon-Lefevre disease ⚠
p.Ser260Pro Single submitter ⚠
p.Ser284Asn Single submitter ⚠
p.Ser284Gly Single submitter Papillon-Lefevre disease ⚠
p.Ser342Ala Single submitter periodontitis, aggressive ⚠
p.Ser45Phe Single submitter periodontitis, aggressive ⚠
p.Ser55Leu Single submitter Inborn genetic diseases ⚠
p.Ser81Tyr Single submitter Inborn genetic diseases ⚠
p.Thr115Ala Single submitter Inborn genetic diseases ⚠
p.Thr115Ile Single submitter Papillon-Lefevre disease ⚠
p.Thr115Pro Single submitter Inborn genetic diseases ⚠
p.Thr189Ile Single submitter Papillon-Lefevre disease ⚠
p.Thr197Ile Single submitter Inborn genetic diseases ⚠
p.Thr280Ile Single submitter Papillon-Lefevre disease ⚠
p.Thr327Pro Single submitter periodontitis, aggressive ⚠
p.Thr327Ser Single submitter Inborn genetic diseases ⚠
p.Trp39Cys Single submitter ⚠
p.Trp429_Gly430insAlaAlaValArgProGlyArgGlnSerGluThrProSerGlnLysLysLysLysLysLysLysLysLysAsnArgTrpGlyXaaXaaXaaXaaLysLysLysLysLysLysLysAsnSerTrp Single submitter periodontitis, aggressive
p.Trp433Ter Single submitter periodontitis, aggressive
p.Tyr107Cys Single submitter Inborn genetic diseases ⚠
p.Tyr150Cys Single submitter Papillon-Lefevre disease ⚠
p.Tyr294Cys Single submitter periodontitis, aggressive ⚠
p.Tyr304His Single submitter Inborn genetic diseases ⚠
p.Tyr32His Single submitter periodontitis, aggressive ⚠
p.Tyr352Cys Single submitter Papillon-Lefevre disease ⚠
p.Tyr99His Single submitter periodontitis, aggressive ⚠
p.Tyr99Phe Single submitter Papillon-Lefevre disease ⚠
p.Val114Leu Single submitter periodontitis, aggressive ⚠
p.Val129Glu Single submitter Haim-Munk syndrome ⚠
p.Val240Ala Single submitter Inborn genetic diseases ⚠
p.Val240Gly Single submitter Papillon-Lefevre disease ⚠
p.Val288Leu Single submitter Inborn genetic diseases ⚠
p.Val348Ile Single submitter Inborn genetic diseases ⚠
p.Val365Ala Single submitter Haim-Munk syndrome ⚠
p.Val43Leu Single submitter periodontitis, aggressive ⚠
p.Val56Ile Single submitter Inborn genetic diseases ⚠