Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Foundation for Research in Genetics and Endocrinology, |
RCV000207246 | SCV000262574 | pathogenic | Tay-Sachs disease | 2011-10-02 | criteria provided, single submitter | clinical testing | This variant found to be pathogenic by online software including Mutation taster, Polyphen2, SIFT. |
Invitae | RCV000207246 | SCV000945208 | pathogenic | Tay-Sachs disease | 2021-07-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asp322 amino acid residue in HEXA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22390110, 22723944, 23852624). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 221280). This variant has been observed in individual(s) with Tay-Sachs disease (PMID: 22723944, 23852624). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with asparagine at codon 322 of the HEXA protein (p.Asp322Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. |