Submissions for variant NM_002474.3(MYH11):c.2472C>T (p.Ala824=)

gnomAD frequency: 0.26411  dbSNP: rs1050113

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000126936	SCV000170467	benign	not specified	2012-11-05	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000126936	SCV000269265	benign	not specified	2013-04-04	criteria provided, single submitter	clinical testing	Ala831Ala in exon 21 of MYH11: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 32.2% (2769/8600) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1050113).
PreventionGenetics, part of Exact Sciences	RCV000126936	SCV000306170	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000245386	SCV000317693	benign	Familial thoracic aortic aneurysm and aortic dissection	2015-02-19	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Illumina Laboratory Services, Illumina	RCV001094377	SCV000395367	benign	Aortic aneurysm, familial thoracic 4	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.
Ambry Genetics	RCV000621372	SCV000738269	benign	Cardiovascular phenotype	2014-11-24	criteria provided, single submitter	clinical testing	This alteration is classified as 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	RCV000245386	SCV000902548	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-16	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000245386	SCV001334005	benign	Familial thoracic aortic aneurysm and aortic dissection	2019-04-08	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001094377	SCV001717666	benign	Aortic aneurysm, familial thoracic 4	2025-02-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001094377	SCV002014373	benign	Aortic aneurysm, familial thoracic 4	2021-09-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001775605	SCV002014374	benign	Megacystis-microcolon-intestinal hypoperistalsis syndrome 2	2021-09-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001775606	SCV002014377	benign	Visceral myopathy 2	2021-09-05	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000245386	SCV004823562	benign	Familial thoracic aortic aneurysm and aortic dissection	2024-10-03	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV004714494	SCV005290202	benign	not provided		criteria provided, single submitter	not provided