Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000004107 | SCV001389887 | pathogenic | Tay-Sachs disease | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 420 of the HEXA protein (p.Trp420Cys). This variant is present in population databases (rs121907958, gnomAD 0.003%). This missense change has been observed in individual(s) with HEXA-related conditions (PMID: 2144098, 14566483; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 3901). 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%. Experimental studies have shown that this missense change affects HEXA function (PMID: 2144098). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000004107 | SCV000024273 | affects | Tay-Sachs disease | 1990-09-01 | no assertion criteria provided | literature only |