Submissions for variant NM_002474.3(MYH11):c.453G>A (p.Pro151=)

gnomAD frequency: 0.00242  dbSNP: rs61734199

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000182487	SCV000234832	benign	not specified	2014-09-18	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.
PreventionGenetics, part of Exact Sciences	RCV000182487	SCV000306196	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000248164	SCV000319391	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2015-01-20	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.
Illumina Laboratory Services, Illumina	RCV000472086	SCV000395400	likely benign	Aortic aneurysm, familial thoracic 4	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae	RCV000472086	SCV000556103	benign	Aortic aneurysm, familial thoracic 4	2024-01-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586758	SCV000697647	benign	not provided	2016-09-26	criteria provided, single submitter	clinical testing	Variant summary: The MYH11 c.453G>A (p.Pro151Pro) variant causes a synonymous change with 5/5 splice prediction tools predicting no significant impact on normal splicing and the removal of an ESE binding site, however, these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 104/121408 (1/1167), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic MYH11 variant of 1/769230, suggesting this variant is likely a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications, however, a clinical diagnostic laboratory cites the variant as "benign." Therfore, the variant of interest has been classified as Benign.
Eurofins Ntd Llc (ga)	RCV000182487	SCV000702027	benign	not specified	2016-10-11	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000618000	SCV000738374	likely benign	Cardiovascular phenotype	2015-07-20	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000472086	SCV000745488	likely benign	Aortic aneurysm, familial thoracic 4	2017-06-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000586758	SCV000884171	benign	not provided	2018-06-29	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000248164	SCV000902169	benign	Familial thoracic aortic aneurysm and aortic dissection	2017-05-15	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000248164	SCV000904562	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-10-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000586758	SCV001249521	likely benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	MYH11: BP4, BP7
All of Us Research Program, National Institutes of Health	RCV000248164	SCV004816856	benign	Familial thoracic aortic aneurysm and aortic dissection	2024-02-05	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000472086	SCV000745978	benign	Aortic aneurysm, familial thoracic 4	2017-01-11	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000182487	SCV002033904	benign	not specified		no assertion criteria provided	clinical testing