ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.532C>T (p.Arg178Cys) (rs121907953)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000416435 SCV001208615 likely pathogenic Tay-Sachs disease 2019-03-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 178 of the HEXA protein (p.Arg178Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs121907953, ExAC 0.003%). This variant has been observed in combination with another HEXA variant in an individual affected with hexosaminidase A deficiency (PMID: 27896118) and in another individual affected with this condition for whom no second allele was reported (PMID: 2137287). ClinVar contains an entry for this variant (Variation ID: 3897). This variant has been reported to affect HEXA protein function (PMID: 2137287). This variant disrupts the p.Arg178 amino acid residue in HEXA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10584247, 17015493, 14577003, 16088929). This suggests that this residue is clinically-significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000004102 SCV000024268 pathogenic Tay-Sachs disease, B1 variant 1990-02-01 no assertion criteria provided literature only
OMIM RCV000004103 SCV000024269 pathogenic HEXA, Czechoslovakian allele 1990-02-01 no assertion criteria provided literature only
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000416435 SCV000494211 pathogenic Tay-Sachs disease 2012-08-23 no assertion criteria provided research

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