Submissions for variant NM_000257.4(MYH7):c.4005G>A (p.Ser1335=)

gnomAD frequency: 0.00064  dbSNP: rs144465613

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Cardiomyopathy Variant Curation Expert Panel	RCV000758055	SCV000564480	benign	Cardiomyopathy	2016-12-15	reviewed by expert panel	curation	The filtering allele frequency of the c.4005G>A (p.Ser1335=) variant in the MYH7 gene is 0.19% (140/64766) 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	RCV000035882	SCV000059533	likely benign	not specified	2015-08-21	criteria provided, single submitter	clinical testing	p.Ser1335Ser in exon 30 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 0.2% (140/64766) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs144465613).
GeneDx	RCV000035882	SCV000170531	benign	not specified	2015-01-05	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	RCV000476016	SCV000557950	benign	Hypertrophic cardiomyopathy	2024-01-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621742	SCV000740106	likely benign	Cardiovascular phenotype	2017-01-05	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.
Color Diagnostics, LLC DBA Color Health	RCV000758055	SCV001353513	benign	Cardiomyopathy	2018-11-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000035882	SCV001737790	likely benign	not specified	2021-06-13	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002496543	SCV002805893	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	2021-08-31	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035882	SCV001920615	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000035882	SCV001953242	benign	not specified		no assertion criteria provided	clinical testing