ClinVar Miner

Submissions for variant NM_001318825.1(HEXA):c.1544G>A (p.Arg515His) (rs121907955)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409695 SCV000485766 likely pathogenic Tay-Sachs disease 2016-02-12 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000409695 SCV000845532 likely pathogenic Tay-Sachs disease 2018-08-07 criteria provided, single submitter clinical testing
Invitae RCV000409695 SCV000950222 pathogenic Tay-Sachs disease 2018-10-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 504 of the HEXA protein (p.Arg504His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous or in combination with other HEXA variants in individuals affected with Tay–Sachs disease (PMID: 8044648, 16088929, 2140574, 21567908). ClinVar contains an entry for this variant (Variation ID: 3895). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg504 amino acid residue in HEXA. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 1837283, 19091716, 25860343), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004099 SCV000024265 pathogenic Gm2-gangliosidosis, juvenile 1991-01-01 no assertion criteria provided literature only

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