Submissions for variant NM_002474.3(MYH11):c.291C>T (p.Asn97=)

gnomAD frequency: 0.00106  dbSNP: rs113363750

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000126974	SCV000170505	benign	not specified	2013-05-29	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.
Ambry Genetics	RCV000617088	SCV000317717	likely benign	Cardiovascular phenotype	2016-02-04	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	RCV000466039	SCV000395404	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.
Invitae	RCV000466039	SCV000556111	benign	Aortic aneurysm, familial thoracic 4	2024-01-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588190	SCV000604344	benign	not provided	2022-03-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588190	SCV000697642	benign	not provided	2016-12-05	criteria provided, single submitter	clinical testing	Variant summary: The MYH11 c.291C>T (p.Asn97Asn) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a damaging outcome for this substitution while 5/5 splice prediction tools predict the variant not to impact normal splicing. This variant was found in 235/121412 control chromosomes, predominantly observed in the South Asian subpopulation at a frequency of 0.0050872 (84/16512). This frequency greatly exceeds the estimated maximal expected allele frequency of a pathogenic MYH11 variant (0.0000013), suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. The variant of interest has not, to our knowledge, been reported in affected individuals with strong evidence for causality; nor evaluated for functional impact by in vivo/vitro studies. Multiple clinical diagnostic laboratories classified this variant as benign. Considering the high prevalence of the variant in the general population, it was classified as benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000251133	SCV000902172	benign	Familial thoracic aortic aneurysm and aortic dissection	2016-06-23	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000251133	SCV000902899	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000588190	SCV002063496	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	MYH11: BP4, BP7