Submissions for variant NM_000257.4(MYH7):c.3036C>T (p.Ala1012=)

gnomAD frequency: 0.00050  dbSNP: rs145379951

Total submissions: 23

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Cardiomyopathy Variant Curation Expert Panel	RCV000758047	SCV000564440	benign	Cardiomyopathy	2016-12-15	reviewed by expert panel	curation	The filtering allele frequency of the c.3036C>T (p.Ala1012=) silent variant in the MYH7 gene is 0.7% (137/16512) of South Asian 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, BP7; PMID:29300372).
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035838	SCV000059489	likely benign	not specified	2012-04-06	criteria provided, single submitter	clinical testing	p.Ala1012Ala in exon 24 of MYH7: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 1/3738 African Am erican chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs145379951).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000204766	SCV000259576	benign	Hypertrophic cardiomyopathy	2025-02-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000242322	SCV000318949	likely benign	Cardiovascular phenotype	2015-09-28	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.
Illumina Laboratory Services, Illumina	RCV000314574	SCV000386077	likely benign	Left ventricular noncompaction cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000366944	SCV000386078	benign	MYH7-related skeletal myopathy	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	RCV003320061	SCV000386079	likely benign	Myosin storage myopathy	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 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	RCV001094176	SCV000386080	likely benign	Hypertrophic cardiomyopathy 1	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 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	RCV000357420	SCV000386081	likely benign	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000035838	SCV000595883	likely benign	not specified	2016-05-05	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000035838	SCV000856902	benign	not specified	2017-09-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000758047	SCV000910861	benign	Cardiomyopathy	2018-03-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000857733	SCV001149182	likely benign	not provided	2025-06-01	criteria provided, single submitter	clinical testing	MYH7: BP4, BP7, BS2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000035838	SCV001360969	benign	not specified	2019-12-14	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000035838	SCV001433418	benign	not specified	2020-05-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000857733	SCV001889411	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002496540	SCV002808479	benign	Hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myosin storage myopathy; Congenital myopathy with fiber type disproportion; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy	2021-08-02	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000857733	SCV005292247	benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV004528170	SCV000303220	benign	MYH7-related disorder	2020-02-25	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000857733	SCV001740425	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035838	SCV001923386	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000035838	SCV001952127	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000857733	SCV001971413	likely benign	not provided		no assertion criteria provided	clinical testing