Submissions for variant NM_002474.3(MYH11):c.3866T>C (p.Val1289Ala)

gnomAD frequency: 0.03954  dbSNP: rs16967510

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000126945	SCV000170476	benign	not specified	2013-09-25	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	RCV000126945	SCV000269267	benign	not specified	2013-04-04	criteria provided, single submitter	clinical testing	Val1296Ala in exon 30 of MYH11: This variant is not expected to have clinical si gnificance because it has been identified in 6.5% (560/8600) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs16967510).
PreventionGenetics, part of Exact Sciences	RCV000126945	SCV000306183	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000242975	SCV000317340	benign	Familial thoracic aortic aneurysm and aortic dissection	2015-06-19	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	RCV000467652	SCV000395296	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 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	RCV000274667	SCV000395297	likely benign	Lissencephaly, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV000467652	SCV000556100	benign	Aortic aneurysm, familial thoracic 4	2024-02-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001812081	SCV000604334	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000617351	SCV000738315	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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000467652	SCV000744019	benign	Aortic aneurysm, familial thoracic 4	2014-10-09	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000242975	SCV000910547	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-07	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001116427	SCV001274501	benign	Lissencephaly 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
All of Us Research Program, National Institutes of Health	RCV000242975	SCV004821289	benign	Familial thoracic aortic aneurysm and aortic dissection	2024-02-05	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000467652	SCV000745965	benign	Aortic aneurysm, familial thoracic 4	2014-02-04	no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000126945	SCV001971516	benign	not specified		no assertion criteria provided	clinical testing