Submissions for variant NM_006922.4(SCN3A):c.791T>C (p.Ile264Thr)

dbSNP: rs768747448

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001301323	SCV001490487	uncertain significance	not provided	2024-01-17	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 264 of the SCN3A protein (p.Ile264Thr). This variant is present in population databases (rs768747448, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SCN3A-related conditions. ClinVar contains an entry for this variant (Variation ID: 403870). 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 not expected to disrupt SCN3A protein function with a negative predictive value of 80%. 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.
CeGaT Center for Human Genetics Tuebingen	RCV001301323	SCV001747267	uncertain significance	not provided	2021-03-01	criteria provided, single submitter	clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV004796182	SCV005418685	likely pathogenic	Epilepsy, familial focal, with variable foci 4		criteria provided, single submitter	clinical testing	PM2_Supporting+PP3_Strong+PP2+PP4