Submissions for variant NM_000256.3(MYBPC3):c.3106C>T (p.Arg1036Cys)

gnomAD frequency: 0.00128  dbSNP: rs61729664

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000035561	SCV000054762	benign	not specified	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035561	SCV000059211	likely benign	not specified	2015-10-22	criteria provided, single submitter	clinical testing	p.Arg1036Cys in exon 29 of MYBPC3: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence and has been identified in 0.6% (58/9778) of African chromosomes by the Exome Aggre gation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs61729664).
GeneDx	RCV000586186	SCV000207993	likely benign	not provided	2020-12-16	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24503780, 23861362, 22958901, 22763267, 27153395, 25524337, 28679633, 29121657, 25163546)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001085534	SCV000284238	benign	Hypertrophic cardiomyopathy	2024-01-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000252526	SCV000320010	likely benign	Cardiovascular phenotype	2019-02-08	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000035561	SCV000696327	benign	not specified	2020-11-16	criteria provided, single submitter	clinical testing	Variant summary: MYBPC3 c.3106C>T (p.Arg1036Cys) results in a non-conservative amino acid change located in the Immunoglobulin-like domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00042 in 245430 control chromosomes, predominantly at a frequency of 0.0056 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 6 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYBPC3 causing Cardiomyopathy phenotype (0.001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.3106C>T has been reported in the literature in individuals affected with Cardiomyopathy. These reports do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. Ten 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/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000035561	SCV000740364	likely benign	not specified	2017-03-30	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000625353	SCV000745033	likely benign	Hypertrophic cardiomyopathy 4	2017-07-12	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000586186	SCV000842846	benign	not provided	2017-12-21	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771353	SCV000903642	likely benign	Cardiomyopathy	2018-03-05	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852648	SCV000995353	likely benign	Cardiomyopathy; Long QT syndrome	2018-11-28	criteria provided, single submitter	clinical testing
Mendelics	RCV000625353	SCV001138289	benign	Hypertrophic cardiomyopathy 4	2019-05-28	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002482960	SCV002795806	likely benign	Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10	2022-04-12	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035561	SCV001917795	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000586186	SCV001956396	likely benign	not provided		no assertion criteria provided	clinical testing