Submissions for variant NM_000256.3(MYBPC3):c.2497G>A (p.Ala833Thr)

gnomAD frequency: 0.00122  dbSNP: rs199865688

Total submissions: 21

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000148656	SCV000051403	likely benign	Primary familial hypertrophic cardiomyopathy	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035494	SCV000059144	likely benign	not specified	2015-10-27	criteria provided, single submitter	clinical testing	p.Ala833Thr in exon 25 of MYBPC3: The significance of this variant was initially debated, as it was reported in 4 individuals with HCM, 3 of whom carried a seco nd variant (Morner 2003, Alders 2003, Andersen 2004, Van Driest 2004). Our labor atory has identified this variant in multiple individuals with various types of cardiomyopathies (HCM, DCM, and LVNC), some of whom also carried a second varian t. The frequent occurrence of a variant in conjunction with additional disease-c ausing variants argues against a pathogenic role when present in isolation as do es its identification in individuals with HCM, LVNC and DCM as these cardiomyopa thies are caused by different defects at the cellular level. Finally, this varia nt has been identified in 0.2% (182/66666) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs199865688) . In summary, the overall evidence suggests that the p.Ala833Thr variant is like ly benign, though we cannot rule out that it may modify disease severity when pr esent with other cardiomyopathy variants.
GeneDx	RCV000234059	SCV000208097	likely benign	not provided	2022-05-10	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Invitae	RCV001081856	SCV000284228	likely benign	Hypertrophic cardiomyopathy	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000617236	SCV000735119	likely benign	Cardiovascular phenotype	2019-03-26	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.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000054796	SCV000883091	uncertain significance	Left ventricular noncompaction 10	2018-11-21	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771175	SCV000903107	likely benign	Cardiomyopathy	2018-03-23	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000234059	SCV001148273	uncertain significance	not provided	2021-03-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000054797	SCV001265541	uncertain significance	Hypertrophic cardiomyopathy 4	2018-03-22	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000771175	SCV001332992	likely benign	Cardiomyopathy	2023-03-06	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000234059	SCV001473884	likely benign	not provided	2021-06-11	criteria provided, single submitter	clinical testing
OMIM	RCV002508762	SCV000083041	pathogenic	Cardiomyopathy, dilated, 1MM	2010-04-01	no assertion criteria provided	literature only
OMIM	RCV000054797	SCV000083042	pathogenic	Hypertrophic cardiomyopathy 4	2010-04-01	no assertion criteria provided	literature only
Blueprint Genetics	RCV000143914	SCV000188787	likely benign	Paroxysmal atrial fibrillation	2014-09-04	no assertion criteria provided	clinical testing
CSER _CC_NCGL, University of Washington	RCV000148656	SCV000190372	likely benign	Primary familial hypertrophic cardiomyopathy	2014-06-01	no assertion criteria provided	research
Blueprint Genetics	RCV000157313	SCV000207048	likely benign	Primary dilated cardiomyopathy	2014-09-04	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000234059	SCV001739972	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000234059	SCV001917719	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000234059	SCV001926945	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000234059	SCV001953851	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000234059	SCV001966400	likely benign	not provided		no assertion criteria provided	clinical testing