ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.5504T>C (p.Ile1835Thr) (rs45563942)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000058788 SCV000884489 likely benign not provided 2018-03-20 criteria provided, single submitter clinical testing The SCN5A c.5507T>C; p.Ile1836Thr variant (rs45563942, ClinVar variant ID 39445) has been reported to segregate with dilated cardiomyopathy in one family (Hershberger 2008), but was also detected in a healthy control individual (Kapa 2009), and several subsequent studies have concluded that the frequency of this variant in the population is inconsistent with a causative role in disease (Amendola 2015, Dorschner 2013, Nourhavesh 2016, Olfson 2015). This variant is listed in the genome Aggregation Database (gnomAD) with an African population frequency of 0.3% (identified on 73 out of 24,028 chromosomes). The isoleucine at position 1836 is highly conserved, considering 9 species, and computational analyses of the effects of the p.Ile1836Thr variant on protein structure and function predict a deleterious effect (SIFT: damaging, PolyPhen-2: possibly damaging). Based on the available information, the p.Ile1836Thr variant is likely to be benign.
Ambry Genetics RCV000621032 SCV000736441 uncertain significance Cardiovascular phenotype 2017-09-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
CSER_CC_NCGL; University of Washington Medical Center RCV000148847 SCV000190590 uncertain significance Primary dilated cardiomyopathy 2014-06-01 no assertion criteria provided research
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058788 SCV000090308 not provided not provided no assertion provided literature only This variant has been reported in the following publications (PMID:19841300;PMID:20129283;PMID:19412328).
GeneDx RCV000212993 SCV000235619 likely benign not specified 2017-11-28 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000458526 SCV000557109 likely benign Brugada syndrome 2017-12-13 criteria provided, single submitter clinical testing
OMIM RCV000032640 SCV000056403 pathogenic Dilated cardiomyopathy 1E 2008-05-01 no assertion criteria provided literature only

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