ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.6007T>C (p.Phe2003Leu) (rs41311117)

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Total submissions: 25
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171818 SCV000050838 benign Long QT syndrome; Brugada syndrome 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041636 SCV000065332 likely benign not specified 2012-03-19 criteria provided, single submitter clinical testing Phe2004Leu in exon 28 of SCN5A: This variant is not expected to have clinical si gnificance because it has been identified in 0.3% (21/6776) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs41311117). Phe2004Leu in exon 28 of SCN5A (rs41311117; allele frequency = 0.3%, 21/6776) **
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000041636 SCV000228662 likely benign not specified 2014-10-17 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000202785 SCV000257780 likely benign Brugada syndrome 1; Long QT syndrome 3 2015-05-11 criteria provided, single submitter clinical testing
Invitae RCV001082610 SCV000259928 benign Brugada syndrome 2020-12-06 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000058821 SCV000280965 likely benign not provided 2015-06-19 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Ambry Genetics RCV000251940 SCV000318496 likely benign Cardiovascular phenotype 2018-11-16 criteria provided, single submitter clinical testing In silico models in agreement (benign);No disease association in small case-control study;Subpopulation frequency in support of benign classification
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000041636 SCV000747931 uncertain significance not specified 2017-02-23 criteria provided, single submitter clinical testing
Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues RCV000678922 SCV000805129 uncertain significance Brugada syndrome 1 2017-12-07 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000058821 SCV000843727 likely benign not provided 2018-04-11 criteria provided, single submitter clinical testing
Color Health, Inc RCV000776090 SCV000910859 likely benign Arrhythmia 2018-03-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000041636 SCV000920195 likely benign not specified 2020-12-07 criteria provided, single submitter clinical testing Variant summary: SCN5A c.6010T>C (p.Phe2004Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0021 in 213020 control chromosomes. The observed variant frequency is approximately 21- fold the estimated maximal expected allele frequency for a pathogenic variant in SCN5A causing Arrhythmia phenotype (0.0001), strongly suggesting that the variant is benign. c.6010T>C has been reported in the literature in individuals affected with sudden death, cardiomyopathies, Long-QT syndrome, and myocarditis (examples: Arnestead_2007, Belkaya_2017, Petrikin_2018, Marcondes_2018, Raju_2019, Mahdieh_2020), but also in healthy controls (examples: Kapplinger_2010, Ghouse_2017). These reports do not provide unequivocal conclusions about association of the variant with Arrhythmia. At least one publication reports experimental evidence indicating that the variant could affect SCN5A function (example: Wang_2007), however a large Danish population study did not identify an association between this variant and cardiac conditions (Ghouse_2017). 12 other ClinVar submitters (evaluation after 2014) cited the variant as uncertain significance (n=4) and benign/ likely benign (n=8). Based on the evidence outlined above, the variant was classified as likely benign.
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852960 SCV000995709 likely benign Cardiomyopathy 2019-01-10 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000058821 SCV001153853 likely benign not provided 2021-09-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001145574 SCV001306262 uncertain significance Dilated cardiomyopathy 1E 2018-03-20 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV000678922 SCV001306263 uncertain significance Brugada syndrome 1 2018-03-20 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.
Illumina Clinical Services Laboratory,Illumina RCV001145575 SCV001306264 benign Sick sinus syndrome 1, autosomal recessive 2018-03-20 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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001145687 SCV001306380 uncertain significance Progressive familial heart block, type 1A 2018-03-20 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001145688 SCV001306381 uncertain significance Long QT syndrome 3 2018-03-20 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001145689 SCV001306382 uncertain significance Paroxysmal familial ventricular fibrillation 1 2018-03-20 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx RCV000058821 SCV001795222 likely benign not provided 2021-05-04 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 33131149, 31737537, 31043699, 31337358, 29672598, 29728395, 28359509, 27711072, 18456723, 17605181, 15851227, 20129283, 23414114, 23465283, 17210841, 22685113)
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058821 SCV000090341 not provided not provided no assertion provided literature only This variant has been reported in the following publications (PMID:15851227;PMID:17210839;PMID:18071069;PMID:18456723;PMID:19841300;PMID:17605181;PMID:20129283).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000058821 SCV001744811 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000058821 SCV001930655 likely benign not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000058821 SCV001960030 likely benign not provided no assertion criteria provided clinical testing

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