Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002043816 | SCV002312259 | uncertain significance | Brugada syndrome | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 1755 of the SCN10A protein (p.Ala1755Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs371924465, ExAC 0.003%). This missense change has been observed in individual(s) with small fiber neuropathy (PMID: 25250524). 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 SCN10A protein function. 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. |