ClinVar Miner

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

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Total submissions: 5
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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

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