ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.1852C>T (p.Leu618Phe) (rs45488304)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000154842 SCV000204524 likely benign not specified 2015-06-05 criteria provided, single submitter clinical testing p.Leu618Phe in exon 12 of SCN5A: This variant is not expected to have clinical s ignificance because it has been identified in 0.6% (59/9220) of African chromoso mes by the Exome Aggregation Consortium (ExAC,; d bSNP rs45488304).
GeneDx RCV000154842 SCV000235387 benign not specified 2017-03-17 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 RCV001085259 SCV000291784 benign Brugada syndrome 2020-11-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV000618998 SCV000735635 likely benign Cardiovascular phenotype 2018-11-29 criteria provided, single submitter clinical testing Other data supporting benign classification;Subpopulation frequency in support of benign classification
Athena Diagnostics Inc RCV000058456 SCV000843711 benign not provided 2018-02-20 criteria provided, single submitter clinical testing
Color Health, Inc RCV000777740 SCV000913700 benign Arrhythmia 2018-10-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000154842 SCV000918193 benign not specified 2018-05-29 criteria provided, single submitter clinical testing Variant summary: SCN5A c.1852C>T (p.Leu618Phe) results in a non-conservative amino acid change located in the Voltage-gated Na+ ion channel, cytoplasmic domain (IPR024583) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The observed variant frequency within African control individuals in the gnomAD database is approximately 216 fold of the estimated maximal expected allele frequency for a pathogenic variant in SCN5A causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. The variant, c.1852C>T, has been reported in the literature in individuals affected with sudden unexplained death (SUD)( Wang_2014 ), Brugada syndrome (Amin_2009), atrial fibrillation (Darbar_2008), and long QT syndrome (Tester_2005). These report(s) do not provide unequivocal conclusions about association of the variant with Cardiomyopathy, Brugada syndrome, atrial fibrillation, Long QT, or SCD. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (Yang_2002). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign (2x) and likely benign (2x). Based on the evidence outlined above, the variant was classified as Benign.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000058456 SCV000987524 likely benign not provided criteria provided, single submitter clinical testing
Mendelics RCV000987220 SCV001136469 benign Brugada syndrome 1 2019-05-28 criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058456 SCV000089976 not provided not provided no assertion provided literature only This variant has been reported in the following publications (PMID:11997281;PMID:14760488;PMID:15840476;PMID:19841300;PMID:20129283;PMID:12673799;PMID:22378279).
CSER _CC_NCGL, University of Washington RCV000148843 SCV000190584 likely benign Long QT syndrome, drug-associated 2014-06-01 no assertion criteria provided research

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