Submissions for variant NM_198056.2(SCN5A):c.1109C>T (p.Thr370Met) (rs199473099)

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color	RCV001189139	SCV001356353	uncertain significance	Arrhythmia	2019-11-08	criteria provided, single submitter	clinical testing
Invitae	RCV001239915	SCV001412818	uncertain significance	Brugada syndrome	2019-11-06	criteria provided, single submitter	clinical testing	This sequence change replaces threonine with methionine at codon 370 of the SCN5A protein (p.Thr370Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of long QT syndrome or who suffered sudden death (PMID: 18508782, 16712702, 19716085, 23631430). However, in one of these individuals pathogenic allele[s] were also identified in KCNQ1, which suggests that this c.1109C>T variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 67636). 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. 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.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute	RCV001256850	SCV001433336	uncertain significance	Dilated cardiomyopathy 1A	2019-03-04	criteria provided, single submitter	clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust	RCV000058393	SCV000089913	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:16712702;PMID:18508782;PMID:19716085). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital	RCV000678842	SCV000805031	uncertain significance	Long QT syndrome	2015-07-30	no assertion criteria provided	clinical testing