Submissions for variant NM_000257.4(MYH7):c.189C>T (p.Thr63=)

gnomAD frequency: 0.51584  dbSNP: rs2069540

Total submissions: 25

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Cardiomyopathy Variant Curation Expert Panel	RCV000758063	SCV000564507	benign	Cardiomyopathy	2016-12-15	reviewed by expert panel	curation	The filtering allele frequency of the c.189C>T (p.Thr63=) variant in the MYH7 gene is 61.57% (6532/10394) 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).
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035752	SCV000059403	benign	not specified	2011-07-29	criteria provided, single submitter	clinical testing	This variant is classified as benign because it does not change the amino acid a nd is frequent in the general population (rs2069540 , MAF >1%).
Genetic Services Laboratory, University of Chicago	RCV000035752	SCV000151918	benign	not specified	2013-08-15	criteria provided, single submitter	clinical testing
GeneDx	RCV000035752	SCV000170543	benign	not specified	2012-09-25	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.
PreventionGenetics, part of Exact Sciences	RCV000035752	SCV000303213	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000248228	SCV000317579	benign	Cardiovascular phenotype	2015-06-12	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	RCV000400497	SCV000386342	benign	Dilated cardiomyopathy 1S	2018-01-12	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	RCV000297610	SCV000386343	benign	MYH7-related skeletal myopathy	2018-01-12	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	RCV000352455	SCV000386344	benign	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094133	SCV000386345	benign	Hypertrophic cardiomyopathy 1	2018-01-12	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	RCV003320050	SCV000386346	benign	Myosin storage myopathy	2018-01-12	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.
Color Diagnostics, LLC DBA Color Health	RCV000758063	SCV000910509	benign	Cardiomyopathy	2018-03-15	criteria provided, single submitter	clinical testing
Invitae	RCV000399650	SCV001000151	benign	Hypertrophic cardiomyopathy	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000400497	SCV002016156	benign	Dilated cardiomyopathy 1S	2021-09-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003320050	SCV002016158	benign	Myosin storage myopathy	2021-09-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001778675	SCV002016159	benign	Myopathy, myosin storage, autosomal recessive	2021-09-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003320050	SCV002016160	benign	Myosin storage myopathy	2021-09-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000297610	SCV002016161	benign	MYH7-related skeletal myopathy	2021-09-05	criteria provided, single submitter	clinical testing
Cohesion Phenomics	RCV000758063	SCV003803016	benign	Cardiomyopathy	2022-10-10	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355869	SCV001550880	uncertain significance	not provided		no assertion criteria provided	clinical testing	13 reputable source/s reports the variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation. Allele frequency is common in at least one population database (frequency: 62.844% in ExAC) based on the frequency threshold of 0.637% for this gene. Variant was observed in a homozygous state in population databases more than expected for disease. A synonymous variant not located in a splice region.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000035752	SCV001744563	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035752	SCV001919243	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000035752	SCV001931759	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000035752	SCV001957987	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000035752	SCV001973709	benign	not specified		no assertion criteria provided	clinical testing