ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.2770G>A (p.Val924Ile) (rs199473177)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041611 SCV000065307 uncertain significance not specified 2012-12-07 criteria provided, single submitter clinical testing The Val924Ile variant in SCN5A has been reported in 2/2600 individuals in a broa d, though clinically and racially unspecified control population (Kapa 2009, Kap plinger 2010). It has not been detected in large and broad European American and African American populations screened by the NHLBI Exome Sequencing Project (ht tp:// although it remains possible that it is common i n other populations. This variant is also listed in dbSNP without frequency dat a (dbSNP rs199473177). The affected amino acid is not completely conserved in ev olution with 1 species naturally carrying the variant. This raises the possibil ity that the change is milder or benign. Of note, the variant is located in a d omain that is believed to be enriched in variants that are present in controls a lthough this does not rule out a pathogenic role (Kapa2009). Additional informat ion is needed to determine clinical significance of this variant.
GeneDx RCV000058525 SCV000235418 likely benign not provided 2019-01-14 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 20129283, 19841300)
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000238603 SCV000297009 uncertain significance Long QT syndrome 3; Brugada syndrome 2015-08-24 criteria provided, single submitter clinical testing
Invitae RCV001085097 SCV000557122 likely benign Brugada syndrome 2020-11-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000058525 SCV000700029 likely benign not provided 2016-11-22 criteria provided, single submitter clinical testing Variant summary: The SCN5A c.2770G>A (p.Val924Ile) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome for this substitution (SNPs&GO not captured due to low reliability index). This variant was found in 18/119070 control chromosomes, predominantly observed in the South Asian subpopulation at a frequency of 0.0009805 (15/15298). This frequency is about 6 times the estimated maximal expected allele frequency of a pathogenic SCN5A variant (0.0001667), suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance, however these classifications predate the ExAC database, when information about the occurrence of the variant in the South Asian population was not available. Considering the prevalence of the variant in the South Asian population, it was classified as likely benign.
Color Health, Inc RCV001179544 SCV001344234 likely benign Arrhythmia 2019-11-24 criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058525 SCV000090045 not provided not provided no assertion provided literature only This variant has been reported in the following publications (PMID:19841300;PMID:20129283).
Blueprint Genetics RCV000157486 SCV000207231 uncertain significance Ventricular tachycardia 2014-05-07 no assertion criteria provided clinical testing

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