Submissions for variant NM_000256.3(MYBPC3):c.1721G>A (p.Arg574Gln)

gnomAD frequency: 0.00026  dbSNP: rs397515922

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723941	SCV000226724	uncertain significance	not provided	2014-05-26	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV000208484	SCV000264028	uncertain significance	Primary dilated cardiomyopathy	2015-01-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000247360	SCV000320550	likely benign	Cardiovascular phenotype	2023-06-07	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.
Illumina Laboratory Services, Illumina	RCV000321873	SCV000372346	benign	Left ventricular noncompaction 10	2018-01-13	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	RCV001094061	SCV000372348	uncertain significance	Hypertrophic cardiomyopathy 4	2018-01-13	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.
Invitae	RCV000267890	SCV000546490	likely benign	Hypertrophic cardiomyopathy	2024-01-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000723941	SCV000616974	uncertain significance	not provided	2023-06-10	criteria provided, single submitter	clinical testing	Has been reported as a variant of uncertain significance in an individual with cardiomyopathy (Pottinger et al., 2020).; Functional studies have demonstrated that p.(R574Q) does not result in a significant splicing defect (Ito et al., 2017); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33782553, 34935411, 32009526, 28679633)
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000624304	SCV000740354	uncertain significance	Primary familial hypertrophic cardiomyopathy	2016-05-18	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170954	SCV001333609	uncertain significance	Cardiomyopathy	2021-03-05	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001170954	SCV001347632	likely benign	Cardiomyopathy	2020-02-13	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035429	SCV000059077	uncertain significance	not specified	2009-02-26	no assertion criteria provided	clinical testing