Submissions for variant NM_000256.3(MYBPC3):c.643C>T (p.Arg215Cys)

gnomAD frequency: 0.00002  dbSNP: rs397516063

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035653	SCV000059304	uncertain significance	not specified	2014-06-25	criteria provided, single submitter	clinical testing	proposed classification - variant undergoing re-assessment, contact laboratory
Ambry Genetics	RCV000245767	SCV000320166	likely benign	Cardiovascular phenotype	2021-10-21	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.
Invitae	RCV000463175	SCV000558163	likely benign	Hypertrophic cardiomyopathy	2024-01-18	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852654	SCV000995360	likely benign	Cardiomyopathy	2018-03-22	criteria provided, single submitter	clinical testing
Mendelics	RCV000988553	SCV001138317	uncertain significance	Hypertrophic cardiomyopathy 4	2019-05-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000852654	SCV001352035	uncertain significance	Cardiomyopathy	2023-11-02	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with cysteine at codon 215 of the MYBPC3 protein. Computational prediction tool indicates that this variant may have an inconclusive impact on protein structure and function, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in three individuals affected with hypertrophic cardiomyopathy (PMID: 23283745, 30600190, and 33495597). This variant was also reported in one individual who was affected with dilated cardiomyopathy (PMID: 33029862). Some of these individuals also carried a pathogenic variant in the TNNT2 gene that could explain the observed phenotype (PMID: 23283745). This variant has been identified in 28/240996 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000852654	SCV002042224	likely benign	Cardiomyopathy	2020-06-23	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002251947	SCV002523121	uncertain significance	See cases	2021-04-05	criteria provided, single submitter	clinical testing	ACMG classification criteria: PP3
Revvity Omics, Revvity	RCV003133121	SCV003817161	uncertain significance	not provided	2022-04-01	criteria provided, single submitter	clinical testing