Submissions for variant NM_000335.5(SCN5A):c.898G>A (p.Val300Ile)

gnomAD frequency: 0.00001  dbSNP: rs199473088

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003541032	SCV001207720	uncertain significance	not provided	2023-06-16	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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 68056). This missense change has been observed in individual(s) with Brugada syndrome (PMID: 20129283). This variant is present in population databases (rs199473088, gnomAD 0.0009%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 300 of the SCN5A protein (p.Val300Ile).
Color Diagnostics, LLC DBA Color Health	RCV001842419	SCV001355166	likely benign	Cardiac arrhythmia	2019-01-10	criteria provided, single submitter	clinical testing
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000058860	SCV000090380	not provided	Brugada syndrome		no assertion provided	literature only	This variant has been reported as associated with Brugada syndrome in the following publications (PMID:20129283). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.