ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.1734C>T (p.Pro578=) (rs200868190)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000217748 SCV000270822 likely benign not specified 2015-09-10 criteria provided, single submitter clinical testing p.Pro578Pro in exon 12 of SCN5A: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 6/9770 African ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs200868190).
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000725380 SCV000336474 uncertain significance not provided 2015-10-29 criteria provided, single submitter clinical testing
Invitae RCV000725380 SCV000557142 likely benign not provided 2018-09-17 criteria provided, single submitter clinical testing
GeneDx RCV000217748 SCV000718846 likely benign not specified 2017-04-25 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000217748 SCV000918189 likely benign not specified 2018-07-31 criteria provided, single submitter clinical testing Variant summary: SCN5A c.1734C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was observed with an allele frequency of 2.9e-05 in 276564 control chromosomes (gnomAD). The variant was predominantly observed in the African cohort with an allele frequency of 0.00025, which is 2.5-fold higher than the expected allele frequency for a pathogenic SCN5A variant of 0.0001, suggesting the variant is a benign polymorphism found predominantly in populations of African origin. To our knowledge, no occurrence of c.1734C>T in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submissions from other clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely benign" (3x) and "uncertain significance" (1x). Based on the evidence outlined above, the variant was classified as likely benign.
Color Health, Inc RCV001190664 SCV001358218 likely benign Arrhythmia 2019-01-07 criteria provided, single submitter clinical testing
Invitae RCV001459892 SCV001663747 likely benign Brugada syndrome 2020-11-04 criteria provided, single submitter clinical testing

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