ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.3875T>C (p.Phe1292Ser) (rs41311127)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171772 SCV000055220 likely benign Brugada syndrome 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000151781 SCV000200232 uncertain significance not specified 2014-07-23 criteria provided, single submitter clinical testing The Phe1293Ser variant in SCN5A has been reported in 2 individuals with Brugada syndrome (Priori 2002, Sommariva 2012), one of whom carried a frameshift variant in the other copy of SCN5A, but has also been identified in 1/590 Caucasian con trol chromosomes (Ackerman 2004) and in 4/8412 European American chromosomes by the NHLBI Exome Sequencing Project (; dbSNP rs41311 127). This variant has also been identified by our laboratory in 1 Caucasian ind ividual with DCM, who had a pathogenic variant in a different gene. The affected amino acid is poorly conserved in evolution, raising the possibility that a cha nge at this position would be tolerated. Other computational prediction tools do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the Phe1293Ser variant is uncertain.
Invitae RCV000171772 SCV000545025 likely benign Brugada syndrome 2020-12-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000058610 SCV000700035 likely benign not provided 2017-05-30 criteria provided, single submitter clinical testing Variant summary: The SCN5A c.3878T>C (p.Phe1293Ser) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 49/119844 control chromosomes including ExAC at a frequency of 0.0004089, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic SCN5A variant (0.0001667), suggesting this variant is likely a benign polymorphism. This variant has been reported in two Brugada syndrome (BrS) patients and one patient presenting with sodium channelopathy (cardiac symptoms, positive family history, and/or abnormal electrocardiogram) in literature (Priori_2002, Chockalingam_2012, and Sommariva_2013). In one BrS patient, another truncating variant c.3258-3261del4 (p.E1087PfsX57) was also present (Sommariva_2013), supporting benign outcome. It has been also reported as polymorphism from published sources (Kapa_2009, Kapplinger_2010) as it was found in healthy controls of European origin. In ClinVar while two clinical labs have classified this variant as VUS, one lab has classified as likely benign. Taken together, this variant is currently classified as likely benign.
Color Health, Inc RCV000771759 SCV000904417 likely benign Arrhythmia 2019-12-17 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845318 SCV000987360 uncertain significance Primary familial dilated cardiomyopathy criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000058610 SCV001145505 likely benign not provided 2019-07-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001147537 SCV001308366 uncertain significance Brugada syndrome 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000058610 SCV001500310 likely benign not provided 2020-07-01 criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058610 SCV000090130 not provided not provided no assertion provided literature only This variant has been reported in the following publications (PMID:11901046;PMID:15851227;PMID:19841300;PMID:20129283).
CSER _CC_NCGL, University of Washington RCV000417329 SCV000503533 uncertain significance Long QT syndrome 2016-08-01 no assertion criteria provided research Found in patient having exome sequencing for an unrelated indication. No known history of Long QT syndrome.
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000058610 SCV000924950 uncertain significance not provided 2017-01-17 no assertion criteria provided provider interpretation

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.