Submissions for variant NM_002474.3(MYH11):c.2208C>T (p.Ile736=)

gnomAD frequency: 0.07252  dbSNP: rs12931799

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030294	SCV000052961	benign	Familial aortopathy	2011-08-18	criteria provided, single submitter	curation	Converted during submission to Benign.
GeneDx	RCV000126934	SCV000170465	benign	not specified	2012-11-29	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	RCV000126934	SCV000269264	benign	not specified	2013-04-04	criteria provided, single submitter	clinical testing	Ile743Ile in exon 19 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 14.5% (636/4394) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs12931799).
PreventionGenetics, part of Exact Sciences	RCV000126934	SCV000306168	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000243057	SCV000317735	benign	Familial thoracic aortic aneurysm and aortic dissection	2015-02-19	criteria provided, single submitter	clinical testing	General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Illumina Laboratory Services, Illumina	RCV000755577	SCV000395369	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811213	SCV000604336	benign	not provided	2023-11-11	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621360	SCV000738318	benign	Cardiovascular phenotype	2014-11-10	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	RCV000243057	SCV000910551	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-07	criteria provided, single submitter	clinical testing
Invitae	RCV000755577	SCV001723414	benign	Aortic aneurysm, familial thoracic 4	2024-02-01	criteria provided, single submitter	clinical testing