ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.1487C>G (p.Ala496Gly)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003066651 SCV003444820 uncertain significance Tay-Sachs disease 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 496 of the HEXA protein (p.Ala496Gly). This variant is present in population databases (rs373781108, gnomAD 0.02%). 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: 2139666). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HEXA protein function with a positive predictive value of 95%. 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.
Ambry Genetics RCV003066652 SCV003532214 uncertain significance Inborn genetic diseases 2023-12-02 criteria provided, single submitter clinical testing The p.A496G variant (also known as c.1487C>G), located in coding exon 13 of the HEXA gene, results from a C to G substitution at nucleotide position 1487. The alanine at codon 496 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. 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 alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic RCV003481372 SCV004227441 uncertain significance not provided 2022-12-08 criteria provided, single submitter clinical testing PP3, PM3

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