Submissions for variant NM_001040113.2(MYH11):c.5819dup (p.Gln1941fs)

dbSNP: rs747392139

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080935	SCV000285803	benign	Aortic aneurysm, familial thoracic 4	2024-01-21	criteria provided, single submitter	clinical testing
GeneDx	RCV000482351	SCV000565751	likely benign	not specified	2017-11-06	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770685	SCV000902152	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-04-04	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000228343	SCV001150812	uncertain significance	not provided	2019-03-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000770685	SCV001344540	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2019-12-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000482351	SCV001362297	likely benign	not specified	2019-04-01	criteria provided, single submitter	clinical testing	Variant summary: MYH11 c.5819dupC (p.Gln1941ThrfsX20) changes the termination codon and is predicted to lead to an extended protein with additional amino acids added to the normal C-terminus. MYH11 c.5819dupC (p.Gln1941ThrfsX20) causes a frameshift which results in an extension of the protein. The variant allele was found at a frequency of 0.0038 in 81378 control chromosomes, predominantly at a frequency of 0.0048 within the Non-Finnish European subpopulation in the ExAC database. The observed variant frequency within Non-Finnish European control individuals in the ExAC database is approximately 3840 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.5819dupC in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Mayo Clinic Laboratories, Mayo Clinic	RCV000228343	SCV004227528	uncertain significance	not provided	2023-02-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003955317	SCV004767030	likely benign	MYH11-related disorder	2021-09-17	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).