Submissions for variant NM_000257.4(MYH7):c.3960G>A (p.Glu1320=)

gnomAD frequency: 0.00044  dbSNP: rs147797612

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035874	SCV000059525	likely benign	not specified	2011-03-24	criteria provided, single submitter	clinical testing	Glu1320Glu in exon 29 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. Silent variants can disrupt DNA sequence motifs that are im portant for mRNA splicing; however, splicing variants are exceedingly rare in th is gene.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079363	SCV000557949	likely benign	Hypertrophic cardiomyopathy	2024-01-19	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000487693	SCV000574968	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	MYH7: BP4, BP7
Color Diagnostics, LLC DBA Color Health	RCV000771370	SCV000903666	likely benign	Cardiomyopathy	2018-07-09	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001109985	SCV001267369	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	RCV003320071	SCV001267370	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	RCV001114021	SCV001271845	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000771370	SCV001333903	likely benign	Cardiomyopathy	2019-11-21	criteria provided, single submitter	clinical testing
GeneDx	RCV000487693	SCV001940830	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000035874	SCV002571797	likely benign	not specified	2022-08-06	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002354189	SCV002621080	likely benign	Cardiovascular phenotype	2019-01-31	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.
Revvity Omics, Revvity	RCV000487693	SCV003817653	uncertain significance	not provided	2023-03-28	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000771370	SCV004823400	likely benign	Cardiomyopathy	2024-02-05	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000487693	SCV001740140	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000487693	SCV001799810	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035874	SCV001918682	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000487693	SCV001930802	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000487693	SCV001958769	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004534744	SCV004753663	likely benign	MYH7-related disorder	2019-04-18	no assertion criteria provided	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).