ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.486C>T (p.Tyr162=) (rs45489099)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000151807 SCV000200273 benign not specified 2012-03-19 criteria provided, single submitter clinical testing p.Tyr162Tyr in Exon 05 of SCN5A: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence and has been identified in 0.9% (28/3212) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs45489099).
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000151807 SCV000231242 likely benign not specified 2014-09-25 criteria provided, single submitter clinical testing
Invitae RCV001085210 SCV000557123 benign Brugada syndrome 2020-11-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV000621518 SCV000737251 likely benign Cardiovascular phenotype 2016-02-22 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification;Synonymous alterations with insufficient evidence to classify as benign
Athena Diagnostics Inc RCV000713146 SCV000843723 benign not provided 2018-01-24 criteria provided, single submitter clinical testing
Color Health, Inc RCV000777818 SCV000913814 benign Arrhythmia 2018-06-25 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001144575 SCV001305186 benign Long QT syndrome 3 2019-04-23 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 RCV001144576 SCV001305187 uncertain significance Brugada syndrome 1 2019-04-23 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 RCV001144577 SCV001305188 likely benign Progressive familial heart block, type 1A 2019-04-23 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV001144578 SCV001305189 benign Sick sinus syndrome 1, autosomal recessive 2019-04-23 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 RCV001144579 SCV001305190 likely benign Paroxysmal familial ventricular fibrillation 1 2019-04-23 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV001146500 SCV001307249 benign Dilated cardiomyopathy 1E 2019-04-23 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000151807 SCV001363136 benign not specified 2019-06-03 criteria provided, single submitter clinical testing Variant summary: SCN5A c.486C>T alters a conserved nucleotide resulting in a synonymous change. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00062 in 248802 control chromosomes. The observed variant frequency is approximately 25 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 benign. To our knowledge, no occurrence of c.486C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrences with other pathogenic variant(s) have been reported (TTR c.424G>A, p.Val142Ile) at our laboratory providing supporting evidence for a benign role. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (n=3)/likely benign (n=1). Based on the evidence outlined above, the variant was classified as benign.

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