MTSS2 — 249 ClinVar variants

All ClinVar germline MTSS2 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 185 flagged for review →

1 Pathogenic/Likely pathogenic · 1 Likely pathogenic · 6 Conflicting · 4 Benign · 44 Likely benign · 193 Uncertain significance

Full MTSS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 185

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 2

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

MTSS2 p.Arg671Trp Pathogenic/Likely pathogenic Multiple submitters
intellectual developmental disorder with ocular anomalies and distinctive facial features
MTSS2 p.Thr597Met Likely pathogenic No assertion criteria
Global developmental delay

Predictors agree, ClinVar conflicts 5

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

MTSS2 p.Ala290Asp Conflicting Single submitter
MTSS2 p.Ala623Thr Conflicting Single submitter
MTSS2 p.Asp620Asn Conflicting Single submitter
intellectual developmental disorder with ocular anomalies and distinctive facial features
MTSS2 p.Gly294Glu Conflicting Single submitter
MTSS2 p.Pro718Ser Conflicting Single submitter

Predictors lean, ClinVar uncertain 117

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

Predictors split 61

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

All MTSS2 variants

Pathogenic/Likely pathogenic 1

p.Arg671Trp Multiple submitters intellectual developmental disorder with ocular anomalies and distinctive facial features ⚠

Likely pathogenic 1

p.Thr597Met No assertion criteria Global developmental delay ⚠

Conflicting classifications of pathogenicity 6

p.Ala290Asp Single submitter ⚠
p.Ala623Thr Single submitter ⚠
p.Asp620Asn Single submitter intellectual developmental disorder with ocular anomalies and distinctive facial features ⚠
p.Gly294Glu Single submitter ⚠
p.Phe203Leu Single submitter ⚠
p.Pro718Ser Single submitter ⚠

Benign 4

p.Ser252= Multiple submitters
c.-182C>T Single submitter
p.Ala577Val Single submitter
p.Thr549= Single submitter

Likely benign 44

p.Pro712= Multiple submitters
p.Thr181= Multiple submitters
c.1129-16C>A Single submitter
c.466+15G>A Single submitter
p.Ala185= Single submitter
p.Ala189= Single submitter
p.Ala335Thr Single submitter
p.Ala390Thr Single submitter
p.Ala410Pro Single submitter
p.Ala444Thr Single submitter
p.Ala545Thr Single submitter
p.Ala610= Single submitter
p.Ala660= Single submitter
p.Arg308His Single submitter
p.Arg394Gln Single submitter
p.Arg609= Single submitter
p.Arg84= Single submitter
p.Asn739= Single submitter
p.Asp159Glu Single submitter
p.Asp397= Single submitter
p.Asp620Glu Single submitter intellectual developmental disorder with ocular anomalies and distinctive facial features
p.Glu370= Single submitter
p.Gly289Arg Single submitter
p.Gly294Arg Single submitter
p.Gly416= Single submitter
p.Gly603Ser Single submitter
p.Gly654Arg Single submitter
p.His436= Single submitter
p.Leu747= Single submitter
p.Phe511Tyr Single submitter
p.Pro423Leu Single submitter
p.Pro588Leu Single submitter ⚠
p.Pro625Ser Single submitter intellectual developmental disorder with ocular anomalies and distinctive facial features
p.Pro628Leu Single submitter
p.Pro703Thr Single submitter
p.Pro710Thr Single submitter
p.Pro719= Single submitter
p.Ser266= Single submitter
p.Ser282Gly Single submitter
p.Ser411Gly Single submitter
p.Thr317= Single submitter
p.Thr595Met Single submitter
p.Val323Ile Single submitter
p.Val598Met Single submitter

Uncertain significance 193

p.Arg734Cys Multiple submitters ⚠
p.Val368Ile Multiple submitters ⚠
c.291-6C>G Single submitter intellectual developmental disorder with ocular anomalies and distinctive facial features
c.291-8C>T Single submitter
c.831-2A>G Single submitter
p.Ala126Thr Single submitter ⚠
p.Ala311Val Single submitter ⚠
p.Ala314Thr Single submitter ⚠
p.Ala318Ser Single submitter ⚠
p.Ala433Thr Single submitter ⚠
p.Ala444Gly Single submitter ⚠
p.Ala4Gly Single submitter ⚠
p.Ala524Thr Single submitter ⚠
p.Ala537Thr Single submitter ⚠
p.Ala557Thr Single submitter intellectual developmental disorder with ocular anomalies and distinctive facial features ⚠
p.Ala577Thr Single submitter ⚠
p.Ala581Thr Single submitter ⚠
p.Ala631Thr Single submitter ⚠
p.Ala644Ser Single submitter ⚠
p.Ala644Val Single submitter ⚠
p.Ala701_Glu705del Single submitter
p.Ala77Thr Single submitter ⚠
p.Ala77Val Single submitter ⚠
p.Ala98Thr Single submitter ⚠
p.Arg131Leu Single submitter ⚠
p.Arg151Ser Single submitter ⚠
p.Arg187His Single submitter intellectual developmental disorder with ocular anomalies and distinctive facial features ⚠
p.Arg196Cys Single submitter ⚠
p.Arg308Cys Single submitter ⚠
p.Arg319Cys Single submitter
p.Arg319His Single submitter ⚠
p.Arg394Trp Single submitter ⚠
p.Arg398Gln Single submitter ⚠
p.Arg403Gln Single submitter ⚠
p.Arg424Gln Single submitter ⚠
p.Arg424Gly Single submitter intellectual developmental disorder with ocular anomalies and distinctive facial features ⚠
p.Arg426Gln Single submitter ⚠
p.Arg464Gln Single submitter ⚠
p.Arg464Gly Single submitter ⚠
p.Arg464Trp Single submitter ⚠
p.Arg528Cys Single submitter ⚠
p.Arg528His Single submitter ⚠
p.Arg565His Single submitter ⚠
p.Arg575His Single submitter ⚠
p.Arg587Gln Single submitter ⚠
p.Arg609Gln Single submitter ⚠
p.Arg671Gln Single submitter ⚠
p.Arg732Gln Single submitter ⚠
p.Arg734His Single submitter ⚠
p.Arg741Ser Single submitter ⚠
p.Arg745Cys Single submitter ⚠
p.Asn526Thr Single submitter ⚠
p.Asn670Ser Single submitter ⚠
p.Asp21Glu Single submitter ⚠
p.Asp485Gly Single submitter ⚠
p.Asp493Glu Single submitter ⚠
p.Asp495Asn Single submitter ⚠
p.Asp504Glu Single submitter ⚠
p.Asp662Asn Single submitter ⚠
p.Asp717Ala Single submitter ⚠
p.Asp717His Single submitter ⚠
p.Cys365Ser Single submitter ⚠
p.Cys365Tyr Single submitter ⚠
p.Cys482Arg Single submitter intellectual developmental disorder with ocular anomalies and distinctive facial features ⚠
p.Cys615Tyr Single submitter ⚠
p.Gln163Ter Single submitter
p.Gln169Arg Single submitter
p.Gln490Ter Single submitter
p.Gln525Pro Single submitter ⚠
p.Gln666Glu Single submitter ⚠
p.Gln94Arg Single submitter ⚠
p.Glu112fs Single submitter
p.Glu153Gln Single submitter ⚠
p.Glu179Gly Single submitter ⚠
p.Glu192Lys Single submitter ⚠
p.Glu484Lys Single submitter ⚠
p.Glu510Lys Single submitter ⚠
p.Glu621Asp Single submitter ⚠
p.Glu621Lys Single submitter ⚠
p.Glu661Lys Single submitter ⚠
p.Glu676Val Single submitter ⚠
p.Glu721Gln Single submitter ⚠
p.Glu721Lys Single submitter ⚠
p.Glu7Lys Single submitter ⚠
p.Gly295Val Single submitter ⚠
p.Gly382Arg Single submitter ⚠
p.Gly419Arg Single submitter ⚠
p.Gly654Val Single submitter ⚠
p.Gly679Glu Single submitter ⚠
p.Gly684Asp Single submitter ⚠
p.Gly684Ser Single submitter ⚠
p.Gly689Arg Single submitter ⚠
p.Gly69Glu Single submitter ⚠
p.Gly9Ser Single submitter ⚠
p.His236Gln Single submitter ⚠
p.His384Arg Single submitter ⚠
p.His384Asn Single submitter ⚠
p.His436Pro Single submitter
p.His459Asp Single submitter ⚠
p.Ile432Thr Single submitter ⚠
p.Ile564_Thr573del Single submitter
p.Ile584Met Single submitter ⚠
p.Ile727Met Single submitter ⚠
p.Leu155Ile Single submitter ⚠
p.Leu415Met Single submitter ⚠
p.Leu553Arg Single submitter ⚠
p.Leu630Arg Single submitter ⚠
p.Leu681Gln Single submitter ⚠
p.Lys116Thr Single submitter ⚠
p.Lys272Gln Single submitter ⚠
p.Lys396Arg Single submitter ⚠
p.Lys636fs Single submitter
p.Lys636Glu Single submitter ⚠
p.Met723Ile Single submitter ⚠
p.Phe15Tyr Single submitter ⚠
p.Pro235Ser Single submitter ⚠
p.Pro313Leu Single submitter ⚠
p.Pro340Leu Single submitter ⚠
p.Pro488Leu Single submitter ⚠
p.Pro508Leu Single submitter ⚠
p.Pro508Ser Single submitter ⚠
p.Pro509Leu Single submitter ⚠
p.Pro543Ser Single submitter ⚠
p.Pro554Ser Single submitter ⚠
p.Pro572Ser Single submitter ⚠
p.Pro583Arg Single submitter intellectual developmental disorder with ocular anomalies and distinctive facial features ⚠
p.Pro585Leu Single submitter ⚠
p.Pro599Ser Single submitter ⚠
p.Pro625Leu Single submitter ⚠
p.Pro635Ser Single submitter ⚠
p.Pro694Leu Single submitter intellectual developmental disorder with ocular anomalies and distinctive facial features ⚠
p.Pro694Ser Single submitter ⚠
p.Pro696Leu Single submitter ⚠
p.Pro708Ser Single submitter ⚠
p.Pro711His Single submitter ⚠
p.Pro711Thr Single submitter ⚠
p.Pro712Leu Single submitter ⚠
p.Pro719Arg Single submitter ⚠
p.Pro719Leu Single submitter ⚠
p.Pro744Ser Single submitter ⚠
p.Ser141Leu Single submitter ⚠
p.Ser24Asn Single submitter ⚠
p.Ser255Asn Single submitter ⚠
p.Ser269Arg Single submitter ⚠
p.Ser280Arg Single submitter ⚠
p.Ser281Asn Single submitter intellectual developmental disorder with ocular anomalies and distinctive facial features ⚠
p.Ser282Asn Single submitter ⚠
p.Ser300fs Single submitter
p.Ser300Leu Single submitter ⚠
p.Ser309Gly Single submitter ⚠
p.Ser34Cys Single submitter ⚠
p.Ser358Phe Single submitter ⚠
p.Ser362Trp Single submitter ⚠
p.Ser372Thr Single submitter ⚠
p.Ser376Leu Single submitter ⚠
p.Ser515Tyr Single submitter ⚠
p.Ser521Asn Single submitter intellectual developmental disorder with ocular anomalies and distinctive facial features ⚠
p.Ser580Arg Single submitter ⚠
p.Ser580Gly Single submitter ⚠
p.Ser580Ile Single submitter ⚠
p.Ser639Ile Single submitter ⚠
p.Ser647Cys Single submitter ⚠
p.Ser673Thr Single submitter ⚠
p.Ser716Gly Single submitter ⚠
p.Ser716Thr Single submitter ⚠
p.Thr375Pro Single submitter ⚠
p.Thr414Asn Single submitter ⚠
p.Thr452Met Single submitter ⚠
p.Thr486Ile Single submitter ⚠
p.Thr544Ile Single submitter ⚠
p.Thr597Lys Single submitter
p.Thr608Ala Single submitter ⚠
p.Thr643Arg Single submitter ⚠
p.Thr697Ala Single submitter ⚠
p.Thr704Met Single submitter ⚠
p.Thr707Met Single submitter ⚠
p.Thr709Ala Single submitter ⚠
p.Thr71Arg Single submitter ⚠
p.Thr79Ala Single submitter ⚠
p.Tyr469Asn Single submitter ⚠
p.Tyr618del Single submitter
p.Tyr655Ter Single submitter
p.Val208Met Single submitter ⚠
p.Val331Ala Single submitter ⚠
p.Val331Ile Single submitter ⚠
p.Val381Gly Single submitter ⚠
p.Val499Met Single submitter ⚠
p.Val561Met Single submitter ⚠
p.Val574Met Single submitter ⚠
p.Val591Ile Single submitter ⚠
p.Val616Ile Single submitter ⚠
p.Val682fs Single submitter
p.Val737Ile Single submitter ⚠