ClinVar Miner

Submissions for variant NM_002471.3(MYH6):c.3010G>T (p.Ala1004Ser) (rs143978652)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000723680 SCV000884189 likely benign not provided 2018-01-22 criteria provided, single submitter clinical testing The c.3010G>T; p.Ala1004Ser variant has been reported in at least five individuals diagnosed with dilated cardiomyopathy (Carniel 2005, Hershberger 2010, Merlo 2013), as well as one patient with arrhythmogenic right ventricular cardiomyopathy (Medeiros-Domingo 2017) and a case of familial atrial septal defects (Posch 2011). However, this variant is listed in the genome Aggregation Database (gnomAD) with a Latino population frequency of 0.2% (identified on 64 out of 34,418 chromosomes), and detailed analysis of ExAC population genetic data suggests the variant is likely to be tolerated (Nouhravesh 2016). Furthermore, this variant was found in two healthy individuals in a study of Europeans between the ages of 55-75 with no sign of cardiac abnormalities (Andreason 2013) and in 3 out of 267 healthy Spanish individuals (0.56%) (Dopazo 2016), and was also detected in healthy family members of the atrial septal defect patient (Posch 2011). It is classified in ClinVar with conflicting interpretations (ID 14151). A functional study showed that expression of this variant in myocytes led to decreased peak sarcomere shortening compared to controls (Klos 2017). Based on the available information, including its prevalence in the general population, the p.Ala1004Ser variant is likely to be benign.
Ambry Genetics RCV000244450 SCV000319519 uncertain significance Cardiovascular phenotype 2018-01-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172563 SCV000051405 likely benign Primary dilated cardiomyopathy 2013-06-24 criteria provided, single submitter research
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770446 SCV000901889 uncertain significance Cardiomyopathy 2017-02-08 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723680 SCV000082834 uncertain significance not provided 2013-06-11 criteria provided, single submitter clinical testing
GeneDx RCV000037468 SCV000513789 likely benign not specified 2017-09-08 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.
Invitae RCV000201499 SCV000557899 likely benign Familial hypertrophic cardiomyopathy 14 2017-12-20 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000037468 SCV000061126 likely benign not specified 2015-07-16 criteria provided, single submitter clinical testing p.Ala1004Ser in exon 23 of MYH6: This variant is not expected to have clinical s ignificance because it has been identified in 0.3% (31/11578) of Latino chromoso mes by the Exome Aggregation Consortium (ExAC,; d bSNP rs143978652).
Laboratory of Genetics and Molecular Cardiology,University of São Paulo RCV000201499 SCV000256193 uncertain significance Familial hypertrophic cardiomyopathy 14 criteria provided, single submitter clinical testing
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000656144 SCV000678338 likely pathogenic Wolff-Parkinson-White pattern 2017-07-14 no assertion criteria provided research This variant was identified in an individual with Wolff-Parkinson-White syndrome
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000623034 SCV000740607 uncertain significance Primary familial hypertrophic cardiomyopathy 2016-06-30 criteria provided, single submitter clinical testing
OMIM RCV000015214 SCV000035471 pathogenic Dilated cardiomyopathy 1EE 2005-07-05 no assertion criteria provided literature only
PreventionGenetics RCV000037468 SCV000308969 likely benign not specified criteria provided, single submitter clinical testing
Scripps Translational Science Institute,Scripps Health and The Scripps Research Institute RCV000190123 SCV000243765 likely pathogenic Familial hypertrophic cardiomyopathy 14; Sudden cardiac death 2015-05-29 criteria provided, single submitter research

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