Submissions for variant NM_002474.3(MYH11):c.3102T>C (p.Ser1034=)

gnomAD frequency: 0.00080  dbSNP: rs181744522

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000249587	SCV000306176	likely benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000769671	SCV000319553	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2015-04-10	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.
Invitae	RCV000556441	SCV000641018	benign	Aortic aneurysm, familial thoracic 4	2024-01-01	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769671	SCV000901082	benign	Familial thoracic aortic aneurysm and aortic dissection	2017-03-13	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000769671	SCV001340858	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-07	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000249587	SCV001361071	benign	not specified	2019-04-16	criteria provided, single submitter	clinical testing	Variant summary: MYH11 c.3123T>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00095 in 251216 control chromosomes, predominantly at a frequency of 0.00064 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 512 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYH11 causing Aortopathy phenotype (1.3e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.3123T>C in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV001579841	SCV001886694	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001579841	SCV001808686	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000249587	SCV001957677	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001579841	SCV001975053	likely benign	not provided		no assertion criteria provided	clinical testing