Submissions for variant NM_002474.3(MYH11):c.3031T>C (p.Leu1011=)

gnomAD frequency: 0.00053  dbSNP: rs112861184

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000182467	SCV000234812	benign	not specified	2014-06-11	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	RCV001000697	SCV000285783	benign	Aortic aneurysm, familial thoracic 4	2024-01-26	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000182467	SCV000306175	likely benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000246269	SCV000319459	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2015-02-27	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Illumina Laboratory Services, Illumina	RCV001000697	SCV000395358	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000680556	SCV000807969	likely benign	Connective tissue disorder	2018-06-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000246269	SCV000913779	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-07-20	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000182467	SCV000917830	benign	not specified	2018-01-08	criteria provided, single submitter	clinical testing	Variant summary: The MYH11 c.3052T>C (p.Leu1018Leu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 121/277210 control chromosomes at a frequency of 0.0004365, which is approximately 349 times the estimated maximal expected allele frequency of a pathogenic MYH11 variant (0.0000013), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV000228093	SCV001150831	likely benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	MYH11: BP4, BP7
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000228093	SCV001157736	likely benign	not provided	2023-09-25	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000246269	SCV002042930	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2020-10-22	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000246269	SCV004821371	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2024-02-05	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000228093	SCV001807084	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000228093	SCV001931941	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000228093	SCV001968122	likely benign	not provided		no assertion criteria provided	clinical testing