ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.1529G>A (p.Arg510Gln)

gnomAD frequency: 0.00001  dbSNP: rs745432499
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001055451 SCV001219844 uncertain significance Tay-Sachs disease 2022-06-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 510 of the HEXA protein (p.Arg510Gln). This variant is present in population databases (rs745432499, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with HEXA-related conditions. ClinVar contains an entry for this variant (Variation ID: 851122). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003331035 SCV004037803 uncertain significance not specified 2023-08-31 criteria provided, single submitter clinical testing Variant summary: HEXA c.1529G>A (p.Arg510Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. Consensus agreement among computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251392 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1529G>A in individuals affected with Tay-Sachs Disease and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters have assessed the variant since 2014, and both classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Natera, Inc. RCV001055451 SCV001460517 uncertain significance Tay-Sachs disease 2020-09-16 no assertion criteria provided clinical testing

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