Submissions for variant NM_000256.3(MYBPC3):c.1246G>A (p.Gly416Ser)

gnomAD frequency: 0.00046  dbSNP: rs371513491

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035380	SCV000059028	uncertain significance	not specified	2016-04-14	criteria provided, single submitter	clinical testing	proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx	RCV001698949	SCV000208005	uncertain significance	not provided	2024-07-14	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21310275, 24503780, 25637381, 21415409, 16858239, 22958901, 25351510, 15519027, 23299917, 28166811, 27532257, 27841901, 30847666, 35130036, 35284542, 32420109, 36166435, 15563892)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000226889	SCV000284208	likely benign	Hypertrophic cardiomyopathy	2025-02-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621944	SCV000736573	likely benign	Cardiovascular phenotype	2023-03-17	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.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000625310	SCV000744855	uncertain significance	Hypertrophic cardiomyopathy 4	2017-05-31	criteria provided, single submitter	clinical testing
Mendelics	RCV000625310	SCV001138307	benign	Hypertrophic cardiomyopathy 4	2019-05-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001184758	SCV001350819	uncertain significance	Cardiomyopathy	2022-12-01	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with serine at codon 416 of the MYBPC3 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional assays have not been performed for this variant. This variant has been reported in individuals affected with hypertrophic cardiomyopathy (PMID: 15519027, 15563892, 27841901), in individuals affected with dilated cardiomyopathy (PMID: 24503780, 35284542, 36166435), as well as in two unaffected individuals (PMID: 15519027). This variant has also been identified in 29/274848 chromosomes (24/23472 African chromosomes) in the general population by the Genome Aggregation Database (gnomAD). The relatively high frequency of this variant in the general population suggests that this variant is unlikely to be disease-causing. However, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health	RCV000226889	SCV004834654	uncertain significance	Hypertrophic cardiomyopathy	2024-07-20	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with serine at codon 416 of the MYBPC3 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <=0.5, PMID: 27666373). To our knowledge, functional assays have not been performed for this variant. This variant has been reported in individuals affected with hypertrophic cardiomyopathy (PMID: 15519027, 15563892, 27841901), in individuals affected with dilated cardiomyopathy (PMID: 24503780, 35284542, 36166435), as well as in two unaffected individuals (PMID: 15519027). This variant has also been identified in 29/274848 chromosomes (24/23472 African chromosomes) in the general population by the Genome Aggregation Database (gnomAD). The relatively high frequency of this variant in the general population suggests that this variant is unlikely to be disease-causing. However, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
CSER _CC_NCGL, University of Washington	RCV000148682	SCV000190407	uncertain significance	Primary familial hypertrophic cardiomyopathy	2014-06-01	no assertion criteria provided	research
Clinical Genetics, Academic Medical Center	RCV001698949	SCV001918661	uncertain significance	not provided		no assertion criteria provided	clinical testing