Submissions for variant NM_002474.3(MYH11):c.914A>G (p.Asn305Ser)

gnomAD frequency: 0.00026  dbSNP: rs185661462

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000182549	SCV000234897	benign	not specified	2016-07-29	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000204065	SCV000261434	benign	Aortic aneurysm, familial thoracic 4	2024-01-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000770694	SCV000317903	benign	Familial thoracic aortic aneurysm and aortic dissection	2017-04-28	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000204065	SCV000744024	likely benign	Aortic aneurysm, familial thoracic 4	2017-07-28	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000204065	SCV000745485	likely benign	Aortic aneurysm, familial thoracic 4	2016-10-20	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659902	SCV000781805	likely benign	Connective tissue disorder	2016-11-01	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770694	SCV000902166	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2016-09-23	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000770694	SCV000911068	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-09-18	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000857860	SCV001150841	likely benign	not provided	2019-06-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000204065	SCV001278179	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000182549	SCV001554564	benign	not specified	2021-03-25	criteria provided, single submitter	clinical testing	Variant summary: MYH11 c.935A>G (p.Asn312Ser) results in a conservative amino acid change located in the Myosin head, motor domain (IPR001609) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00068 in 251434 control chromosomes, predominantly at a frequency of 0.0083 within the East Asian subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 664 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYH11 causing Thoracic Aortic Aneurysms And Dissections phenotype (1.3e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. Nine ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign and one ClinVar submitter (evaluation after 2014) cites it as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000857860	SCV002047958	likely benign	not provided	2021-09-03	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000857860	SCV001807797	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003967452	SCV004781976	likely benign	MYH11-related disorder	2019-03-15	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).