HCCS — 105 ClinVar variants
All ClinVar germline HCCS variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 34 flagged for review →
2 Pathogenic · 10 Likely pathogenic · 5 Conflicting · 12 Benign · 11 Benign/Likely benign · 30 Likely benign · 35 Uncertain significance
Full HCCS gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 34
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 agree, ClinVar conflicts 3
ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.
Predictors lean, ClinVar uncertain 24
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
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HCCS p.Ala19Pro
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
HCCS p.Ala60Thr
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
HCCS p.Ala174Ser
Uncertain significance
Single submitter
linear skin defects with multiple congenital anomalies 1
-
HCCS p.Ala19Val
Uncertain significance
Single submitter
Inborn genetic diseases
-
HCCS p.Arg246Cys
Uncertain significance
Single submitter
linear skin defects with multiple congenital anomalies 1
- HCCS p.Arg59Ser Uncertain significance Single submitter
-
HCCS p.Glu115Gln
Uncertain significance
Single submitter
Inborn genetic diseases
- HCCS p.Glu191Asp Uncertain significance Single submitter
-
HCCS p.Gly231Val
Uncertain significance
Single submitter
linear skin defects with multiple congenital anomalies 1
- HCCS p.Gly30Arg Uncertain significance Single submitter
-
HCCS p.His28Pro
Uncertain significance
Single submitter
Inborn genetic diseases
- HCCS p.Leu243Val Uncertain significance Single submitter
-
HCCS p.Lys190Arg
Uncertain significance
Single submitter
Inborn genetic diseases
- HCCS p.Met202Ile Uncertain significance Single submitter
- HCCS p.Met32Thr Uncertain significance Single submitter
- HCCS p.Pro22Leu Uncertain significance Single submitter
-
HCCS p.Pro44Arg
Uncertain significance
Single submitter
Inborn genetic diseases
-
HCCS p.Pro44Leu
Uncertain significance
Single submitter
Inborn genetic diseases
- HCCS p.Ser82Pro Uncertain significance Single submitter
-
HCCS p.Tyr238His
Uncertain significance
Single submitter
Inborn genetic diseases
- HCCS p.Tyr61Cys Uncertain significance Single submitter
-
HCCS p.Val103Phe
Uncertain significance
Single submitter
Inborn genetic diseases
-
HCCS p.His154Pro
Uncertain significance
No assertion criteria
HCCS-related disorder
- HCCS p.Pro54Leu Uncertain significance No assertion criteria
Predictors split 7
The independent predictors disagree with each other — read with care.
-
HCCS p.Ala262Gly
Benign/Likely benign
Multiple submitters
Inborn genetic diseases
- HCCS p.Asp95His Uncertain significance Single submitter
- HCCS p.Leu79Pro Uncertain significance Single submitter
-
HCCS p.Met147Val
Uncertain significance
Single submitter
HCCS-related disorder
-
HCCS p.Pro36Leu
Conflicting
Single submitter
Inborn genetic diseases
-
HCCS p.Pro67Thr
Uncertain significance
Single submitter
linear skin defects with multiple congenital anomalies 1
-
HCCS p.Pro92Thr
Uncertain significance
Single submitter
Inborn genetic diseases
All HCCS variants
Pathogenic 2
- p.Trp213Ser Single submitter
- p.Arg197Ter No assertion criteria linear skin defects with multiple congenital anomalies 1
Likely pathogenic 10
- p.Arg217Cys Multiple submitters HCCS-related disorder
- p.Trp135Ter Multiple submitters HCCS-related disorders
- c.521+1G>A Single submitter HCCS-related disorders
- p.Ala55fs Single submitter linear skin defects with multiple congenital anomalies 1
- p.Arg217His Single submitter linear skin defects with multiple congenital anomalies 1
- p.Gln239Ter Single submitter linear skin defects with multiple congenital anomalies 1
- p.Met147fs Single submitter HCCS-related disorders
- p.Met1Thr Single submitter linear skin defects with multiple congenital anomalies 1
- p.Trp201Ter Single submitter linear skin defects with multiple congenital anomalies 1
- p.Val103dup Single submitter linear skin defects with multiple congenital anomalies 1
Conflicting classifications of pathogenicity 5
- c.252+5T>G Single submitter
- p.Ala174Val Single submitter ⚠
- p.Asn235Ser Single submitter ⚠
- p.Gly2Asp Single submitter Inborn genetic diseases ⚠
- p.Pro36Leu Single submitter Inborn genetic diseases ⚠
Benign 12
- c.402-331A>G Multiple submitters
- c.101-13T>C Single submitter
- c.253-299G>A Single submitter
- c.608+24_608+26del Single submitter
- p.Ala173Val Single submitter
- p.Arg59= Single submitter
- p.Asn235= Single submitter
- p.Gly2Ser Single submitter
- p.Ile183= Single submitter
- p.Lys163= Single submitter
- p.Tyr63= Single submitter
- p.Val261= Single submitter
Benign/Likely benign 11
- c.101-11G>C Multiple submitters
- c.521+7A>G Multiple submitters
- p.Ala262Gly Multiple submitters Inborn genetic diseases ⚠
- p.Ala72= Multiple submitters History of neurodevelopmental disorder
- p.Ala72Val Multiple submitters Inborn genetic diseases
- p.Arg59Cys Multiple submitters
- p.Asn158= Multiple submitters
- p.Cys218= Multiple submitters
- p.Glu233Lys Multiple submitters linear skin defects with multiple congenital anomalies 1
- p.Ile150Val Multiple submitters Inborn genetic diseases
- p.Val255Ile Multiple submitters Inborn genetic diseases
Likely benign 30
- p.Ala17Ser Multiple submitters Inborn genetic diseases
- c.101-308C>T Single submitter
- c.252+8A>G Single submitter linear skin defects with multiple congenital anomalies 1
- c.402-11T>C Single submitter
- c.608+13G>A Single submitter
- c.609-19T>C Single submitter
- c.-10_-9del Single submitter
- c.*22dup Single submitter
- c.*265T>C Single submitter
- c.*287G>A Single submitter
- p.Ala129= Single submitter
- p.Ala254= Single submitter
- p.Ala7= Single submitter
- p.Ala9Gly Single submitter Inborn genetic diseases
- p.Arg197= Single submitter
- p.Asn16Asp Single submitter Inborn genetic diseases
- p.Glu159= Single submitter
- p.Glu175Ala Single submitter
- p.Glu65= Single submitter
- p.Gly134= Single submitter
- p.His211= Single submitter
- p.Leu131= Single submitter
- p.Met32Leu Single submitter
- p.Met32Val Single submitter Inborn genetic diseases
- p.Pro110= Single submitter
- p.Pro180= Single submitter
- p.Ser268Leu Single submitter
- p.Ser6= Single submitter
- p.Thr102= Single submitter
- p.Tyr224= Single submitter
Uncertain significance 35
- p.Ala19Pro Multiple submitters Inborn genetic diseases ⚠
- p.Ala60Thr Multiple submitters Inborn genetic diseases ⚠
- c.608+5G>C Single submitter linear skin defects with multiple congenital anomalies 1
- p.Ala174Ser Single submitter linear skin defects with multiple congenital anomalies 1 ⚠
- p.Ala19Val Single submitter Inborn genetic diseases ⚠
- p.Arg246Cys Single submitter linear skin defects with multiple congenital anomalies 1 ⚠
- p.Arg59Ser Single submitter ⚠
- p.Asp95His Single submitter ⚠
- p.Glu115Gln Single submitter Inborn genetic diseases ⚠
- p.Glu191Asp Single submitter ⚠
- p.Gly231Val Single submitter linear skin defects with multiple congenital anomalies 1 ⚠
- p.Gly30Arg Single submitter ⚠
- p.His28Pro Single submitter Inborn genetic diseases ⚠
- p.His56Gln Single submitter Inborn genetic diseases
- p.Leu243Val Single submitter ⚠
- p.Leu79Pro Single submitter ⚠
- p.Lys133fs Single submitter
- p.Lys190Arg Single submitter Inborn genetic diseases ⚠
- p.Lys190fs Single submitter
- p.Met147Val Single submitter HCCS-related disorder ⚠
- p.Met202Ile Single submitter ⚠
- p.Met32Thr Single submitter ⚠
- p.Pro22Leu Single submitter ⚠
- p.Pro44Arg Single submitter Inborn genetic diseases ⚠
- p.Pro44Leu Single submitter Inborn genetic diseases ⚠
- p.Pro67Thr Single submitter linear skin defects with multiple congenital anomalies 1 ⚠
- p.Pro92Thr Single submitter Inborn genetic diseases ⚠
- p.Ser268Ter Single submitter
- p.Ser82Pro Single submitter ⚠
- p.Tyr238His Single submitter Inborn genetic diseases ⚠
- p.Tyr61Cys Single submitter ⚠
- p.Val103Phe Single submitter Inborn genetic diseases ⚠
- c.253-3T>G No assertion criteria linear skin defects with multiple congenital anomalies 1
- p.His154Pro No assertion criteria HCCS-related disorder ⚠
- p.Pro54Leu No assertion criteria ⚠