Submissions for variant NM_000257.4(MYH7):c.3153G>A (p.Ala1051=)

gnomAD frequency: 0.00505  dbSNP: rs45540831

Total submissions: 25

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Cardiomyopathy Variant Curation Expert Panel	RCV000758077	SCV000564486	benign	Cardiomyopathy	2016-12-15	reviewed by expert panel	curation	The filtering allele frequency of the c.3153G>A (p.Ala1051=) variant in the MYH7 gene is 0.68% (490/66740) of European chromosomes by the Exome Aggregation Consortium (http://exac.broadinstitute.org), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BA1; PMID:29300372).
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035839	SCV000059490	benign	not specified	2011-06-08	criteria provided, single submitter	clinical testing	This variant is considered to be benign because it does not change an amino acid and is frequent in the general population(rs45540831 ; MAF> 1%)
Eurofins Ntd Llc (ga)	RCV000035839	SCV000228109	benign	not specified	2014-11-14	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000202765	SCV000257657	benign	Hypertrophic cardiomyopathy 1	2015-06-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000226727	SCV000284274	benign	Hypertrophic cardiomyopathy	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000035839	SCV000303221	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000243522	SCV000318992	benign	Cardiovascular phenotype	2015-05-15	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.
Illumina Laboratory Services, Illumina	RCV000202765	SCV000386070	likely benign	Hypertrophic cardiomyopathy 1	2018-03-06	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV000513456	SCV000608694	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	MYH7: BP4, BP7, BS1, BS2
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000513456	SCV000610328	likely benign	not provided	2017-05-02	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000035839	SCV000614143	benign	not specified	2020-10-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000758077	SCV000910660	benign	Cardiomyopathy	2018-03-05	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV003320062	SCV001267552	likely benign	Myosin storage myopathy	2018-03-06	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001110154	SCV001267553	benign	MYH7-related skeletal myopathy	2018-03-06	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.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000035839	SCV001433173	benign	not specified	2019-08-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000513456	SCV001751611	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26332594, 21302287)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000513456	SCV004562922	benign	not provided	2023-10-09	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000513456	SCV005292136	benign	not provided		criteria provided, single submitter	not provided
Genetic Services Laboratory, University of Chicago	RCV000035839	SCV000151920	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000035839	SCV001739900	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000513456	SCV001800730	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035839	SCV001921337	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000035839	SCV001931735	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000035839	SCV001955411	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000035839	SCV001974873	benign	not specified		no assertion criteria provided	clinical testing