ClinVar Miner

Submissions for variant NM_000521.4(HEXB):c.925T>C (p.Cys309Arg)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003609102 SCV004462615 likely pathogenic Sandhoff disease 2023-05-05 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Cys309 amino acid residue in HEXB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7557963, 26582265). 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 HEXB protein function. This variant has not been reported in the literature in individuals affected with HEXB-related conditions. This variant is present in population databases (rs777657769, gnomAD 0.003%). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 309 of the HEXB protein (p.Cys309Arg).

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