Submissions for variant NM_000257.4(MYH7):c.2162+4G>A

gnomAD frequency: 0.00276  dbSNP: rs145738465

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Cardiomyopathy Variant Curation Expert Panel	RCV000758064	SCV000564423	benign	Cardiomyopathy	2016-12-15	reviewed by expert panel	curation	The filtering allele frequency of the c.2162+4G>A variant in the MYH7 gene is 0.75% (93/10406) of African 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). Additionally, computational prediction tools and conservation analysis suggest that this variant may not impact the protein (BP4).
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035769	SCV000059420	likely benign	not specified	2015-03-21	criteria provided, single submitter	clinical testing	c.2162+4G>A in intron 19 of MYH7: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence and has been identified in 0.9% (93/10406) of African chromosomes by the Exome Aggre gation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs145738465). Thi s cohort included 2 individuals who carried this variant in the homozygous state .
Eurofins Ntd Llc (ga)	RCV000035769	SCV000226726	benign	not specified	2015-01-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086617	SCV000252660	benign	Hypertrophic cardiomyopathy	2024-01-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000035769	SCV000303216	likely benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621043	SCV000740037	likely benign	Cardiovascular phenotype	2019-01-03	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.
Athena Diagnostics	RCV000712356	SCV000842830	benign	not provided	2018-01-26	criteria provided, single submitter	clinical testing
Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital	RCV000035769	SCV000864319	likely benign	not specified	2017-10-04	criteria provided, single submitter	clinical testing	BS1, BP4, BP6; This alteration has an allele frequency that is greater than expected for the associated disease, is predicted to be tolerated by multiple functional prediction tools, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory).
Color Diagnostics, LLC DBA Color Health	RCV000758064	SCV000913768	benign	Cardiomyopathy	2018-10-16	criteria provided, single submitter	clinical testing
GeneDx	RCV000712356	SCV001940821	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002504877	SCV002811171	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	2021-07-27	criteria provided, single submitter	clinical testing
Cohesion Phenomics	RCV001086617	SCV003803033	benign	Hypertrophic cardiomyopathy	2022-10-10	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000712356	SCV001744591	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035769	SCV001925924	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000035769	SCV001930480	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000035769	SCV001964424	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000712356	SCV002036504	likely benign	not provided		no assertion criteria provided	clinical testing