Submissions for variant NM_000335.5(SCN5A):c.568C>G (p.Arg190Gly)

gnomAD frequency: 0.00057  dbSNP: rs199473068

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV000157477	SCV000207222	likely benign	not specified	2015-01-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000766778	SCV000235327	uncertain significance	not provided	2013-10-01	criteria provided, single submitter	clinical testing	p.Arg190Gly (CGG>GGG): c.568 C>G in exon 5 of the SCN5A gene (NM_198056.2) The Arg190Gly variant in the SCN5A gene has been reported in three unrelated families from Finland with LQTS, however, it was present in 2/200 healthy Finnish controls (Fodstad H et al., 2004). Fodstad et al. concluded further studies are necessary to determine if Arg190Gly is associated with a LQTS phenotype or if it is a rare benign variant. Arg190Gly results in a non-conservative amino acid substitution of a positively charged Arginine with a non-polar Glycine at a position that is conserved across species. Other mutations in this residue (Arg190Gln) and in nearby residues (Thr187Ile, Ala204Val) have been reported in association with LQTS further supporting the functional importance of this residue and this region of the protein. Furthermore, the Arg190Gly variant was not observed inapproximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. With the clinical and molecular information available at this time, we cannot definitively determine if Arg190Gly is a disease-causing mutation or a rare benign variant. The variant is found in LQT panel(s).
Color Diagnostics, LLC DBA Color Health	RCV001842390	SCV001346736	likely benign	Cardiac arrhythmia	2019-02-25	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000766778	SCV002403981	benign	not provided	2024-10-12	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001842390	SCV004827153	likely benign	Cardiac arrhythmia	2024-09-23	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000766778	SCV005409163	uncertain significance	not provided	2023-09-22	criteria provided, single submitter	clinical testing	BS1, BS3_supporting, PP3
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000058798	SCV000090318	not provided	Congenital long QT syndrome		no assertion provided	literature only	This variant has been reported as associated with Long QT syndrome in the following publications (PMID:15176425;PMID:22402334). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.