Submissions for variant NM_000257.4(MYH7):c.327C>T (p.Tyr109=)

gnomAD frequency: 0.00009  dbSNP: rs36211408

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Cardiomyopathy Variant Curation Expert Panel	RCV000758060	SCV000564504	benign	Cardiomyopathy	2016-12-15	reviewed by expert panel	curation	The filtering allele frequency of the c.327C>T (p.Tyr109=) silent variant in the MYH7 gene is 0.13% (31/16512) 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	RCV000035845	SCV000059496	likely benign	not specified	2015-01-29	criteria provided, single submitter	clinical testing	p.Tyr109Tyr in exon 4 of MYH7: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located nea r a splice junction. It has been identified in 0.2% (31/16512) of South Asian ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs36211408).
Invitae	RCV000205852	SCV000259414	likely benign	Hypertrophic cardiomyopathy	2024-01-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000035845	SCV000516733	benign	not specified	2015-07-08	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.
Ambry Genetics	RCV000619846	SCV000736795	likely benign	Cardiovascular phenotype	2016-11-22	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	RCV000758060	SCV000905092	benign	Cardiomyopathy	2018-10-16	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001113564	SCV001271348	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV001114969	SCV001272896	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	RCV003320064	SCV001272897	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000758060	SCV001333926	benign	Cardiomyopathy	2018-04-26	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001532238	SCV001474027	benign	not provided	2020-03-06	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001532238	SCV001747708	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	MYH7: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003944894	SCV004760388	likely benign	MYH7-related condition	2023-08-01	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).