Submissions for variant NM_000335.5(SCN5A):c.2318C>G (p.Pro773Arg)

dbSNP: rs2061687716

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003656362	SCV001225863	uncertain significance	not provided	2019-02-05	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in an individual affected with clinical features of Brugada syndrome (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with arginine at codon 773 of the SCN5A protein (p.Pro773Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine.
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	RCV001061131	SCV002754561	uncertain significance	Brugada syndrome	2022-02-11	no assertion criteria provided	clinical testing