Submissions for variant NM_000257.4(MYH7):c.1119G>A (p.Ala373=)

gnomAD frequency: 0.00001  dbSNP: rs572672362

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Cardiomyopathy Variant Curation Expert Panel	RCV000758025	SCV000564497	benign	Cardiomyopathy	2016-12-15	reviewed by expert panel	curation	The filtering allele frequency of the c.1119G>A (p.Ala373=) variant in the MYH7 gene is 0.12% (21/11578) of Latino 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).
GeneDx	RCV000127022	SCV000170555	benign	not specified	2014-03-12	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.
Illumina Laboratory Services, Illumina	RCV000271937	SCV000386245	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	RCV003320103	SCV000386246	uncertain significance	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, 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	RCV000367591	SCV000386247	likely benign	Left ventricular noncompaction cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000275351	SCV000386248	likely benign	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094128	SCV000386249	uncertain significance	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, 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.
Invitae	RCV000332655	SCV000557954	benign	Hypertrophic cardiomyopathy	2024-01-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000617831	SCV000735503	likely benign	Cardiovascular phenotype	2016-08-23	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	RCV000758025	SCV001349855	benign	Cardiomyopathy	2018-10-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003422015	SCV004129095	likely benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing	MYH7: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003894985	SCV004722216	likely benign	MYH7-related condition	2019-06-14	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).