Submissions for variant NM_000256.3(MYBPC3):c.977G>A (p.Arg326Gln)

gnomAD frequency: 0.00376  dbSNP: rs34580776

Total submissions: 25

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000190557	SCV000051567	benign	Hypertrophic cardiomyopathy	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035689	SCV000059340	benign	not specified	2010-07-08	criteria provided, single submitter	clinical testing	The Arg326Gln variant is thought to be a common variant found in over 5% of indi viduals from certain populations (Jaaskelainen et al. 2002, dbSNP rs34580786). T herefore, it is highly unlikely that this variant is disease-causing.
GeneDx	RCV000035689	SCV000170458	benign	not specified	2012-06-12	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000190557	SCV000252659	benign	Hypertrophic cardiomyopathy	2024-01-31	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000238837	SCV000296898	benign	Dilated cardiomyopathy 1A	2015-10-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000250801	SCV000317754	benign	Cardiovascular phenotype	2017-08-04	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586999	SCV000696336	benign	not provided	2016-06-06	criteria provided, single submitter	clinical testing	Variant summary: The MYBPC3 c.977G>A (p.Arg326Gln) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome (SNPs&GO not captured due to low reliability index). This variant was found in 521/94034 control chromosomes (3 homozygotes), predominantly observed in the European (Finnish) subpopulation at a frequency of 0.015543 (77/4954). This frequency is about 16 times the estimated maximal expected allele frequency of a pathogenic MYBPC3 variant (0.0010005), suggesting this is likely a benign polymorphism found primarily in the populations of European (Finnish) origin. In addition, the variant was found to co-occur with a pathogenic MYBPC3 variant (Gln1233Ter) in two individuals (Ingles_JMG_2005 and internal LCA data), and was also found in an unaffected sister of an HCM patient (Jaaskelainen_JMM_2002). Furthermore, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000613127	SCV000743565	benign	Hypertrophic cardiomyopathy 4	2014-10-09	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000613127	SCV000744858	benign	Hypertrophic cardiomyopathy 4	2015-09-21	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000035689	SCV000747987	likely benign	not specified	2016-10-26	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000776079	SCV000910815	benign	Cardiomyopathy	2018-03-05	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852653	SCV000995358	likely benign	Primary dilated cardiomyopathy; Premature ventricular contraction	2019-03-25	criteria provided, single submitter	clinical testing
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute	RCV000190557	SCV000996360	benign	Hypertrophic cardiomyopathy	2017-09-22	criteria provided, single submitter	research	This variant has been identified as part of our research program. Refer to the 'condition' field for the phenotype of the proband(s) identified with this variant. For further information please feel free to contact us.
CeGaT Center for Human Genetics Tuebingen	RCV000586999	SCV001148280	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	MYBPC3: BS2
Illumina Laboratory Services, Illumina	RCV000613127	SCV001263316	likely benign	Hypertrophic cardiomyopathy 4	2017-04-27	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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001107678	SCV001264853	benign	Left ventricular noncompaction 10	2017-04-27	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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Fulgent Genetics, Fulgent Genetics	RCV002496538	SCV002805377	likely benign	Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10	2021-08-26	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000586999	SCV004563090	benign	not provided	2023-10-09	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000190557	SCV004834696	benign	Hypertrophic cardiomyopathy	2024-02-05	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV000157304	SCV000207036	likely benign	Primary familial hypertrophic cardiomyopathy	2014-05-16	no assertion criteria provided	clinical testing
Blueprint Genetics	RCV000157305	SCV000207037	likely benign	Primary dilated cardiomyopathy	2014-05-16	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000613127	SCV000733056	benign	Hypertrophic cardiomyopathy 4		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035689	SCV001919629	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000035689	SCV001955481	benign	not specified		no assertion criteria provided	clinical testing
Cohesion Phenomics	RCV000190557	SCV003800601	benign	Hypertrophic cardiomyopathy	2022-10-10	no assertion criteria provided	clinical testing