Submissions for variant NM_000256.3(MYBPC3):c.1566G>A (p.Ala522=)

gnomAD frequency: 0.00016  dbSNP: rs376041792

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035412	SCV000059060	likely benign	not specified	2015-12-04	criteria provided, single submitter	clinical testing	p.Ala522Ala in exon 17 of MYBPC3: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 23/66374 Europea n chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstit ute.org; dbSNP rs376041792).
Invitae	RCV001081419	SCV000558144	likely benign	Hypertrophic cardiomyopathy	2024-01-24	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000488261	SCV000574881	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	MYBPC3: BP4, BP7
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000625309	SCV000744849	likely benign	Hypertrophic cardiomyopathy 4	2017-06-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771847	SCV000904561	likely benign	Cardiomyopathy	2018-10-16	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001103226	SCV001259954	benign	Left ventricular noncompaction 10	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000625309	SCV001259955	uncertain significance	Hypertrophic cardiomyopathy 4	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000771847	SCV001333615	likely benign	Cardiomyopathy	2019-02-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000488261	SCV001848421	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002399368	SCV002709942	likely benign	Cardiovascular phenotype	2018-03-07	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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	RCV000035412	SCV004038000	likely benign	not specified	2023-08-19	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035412	SCV001918336	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000488261	SCV001959987	likely benign	not provided		no assertion criteria provided	clinical testing