Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001901555 | SCV002172348 | uncertain significance | Brugada syndrome | 2021-08-02 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with small fiber neuropathy (PMID: 23986244). 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. Experimental studies have shown that this missense change affects SCN10A protein function (PMID: 23986244, 29992996). 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. This sequence change replaces isoleucine with valine at codon 1706 of the SCN10A protein (p.Ile1706Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. |