ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.581C>T (p.Ala194Val)

gnomAD frequency: 0.00010  dbSNP: rs778947516
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000538820 SCV000629535 uncertain significance Tay-Sachs disease 2022-08-06 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 194 of the HEXA protein (p.Ala194Val). This variant is present in population databases (rs778947516, gnomAD 0.04%). 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: 458318). 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"). 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.
Counsyl RCV000538820 SCV000795678 uncertain significance Tay-Sachs disease 2017-11-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV002358466 SCV002650775 uncertain significance Inborn genetic diseases 2015-06-14 criteria provided, single submitter clinical testing The p.A194V variant (also known as c.581C>T), located in coding exon 6 of the HEXA gene, results from a C to T substitution at nucleotide position 581. The alanine at codon 194 is replaced by valine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6496 samples (12992 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Natera, Inc. RCV000538820 SCV002086293 uncertain significance Tay-Sachs disease 2018-09-11 no assertion criteria provided clinical testing

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