Submissions for variant NM_002474.3(MYH11):c.5439G>A (p.Lys1813=)

gnomAD frequency: 0.44262  dbSNP: rs1050162

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000146505	SCV000170494	benign	not specified	2012-11-02	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000146505	SCV000269273	benign	not specified	2013-04-04	criteria provided, single submitter	clinical testing	Lys1820Lys in exon 39 of MYH11: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 49.2% (4229/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1050162).
PreventionGenetics, part of Exact Sciences	RCV000146505	SCV000306206	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000245108	SCV000317690	benign	Familial thoracic aortic aneurysm and aortic dissection	2015-06-19	criteria provided, single submitter	clinical testing	General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Illumina Laboratory Services, Illumina	RCV000245108	SCV000395211	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000304468	SCV000395212	benign	Lissencephaly 4	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Ambry Genetics	RCV000622103	SCV000738275	benign	Cardiovascular phenotype	2014-11-19	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000601977	SCV000745474	benign	Aortic aneurysm, familial thoracic 4	2017-06-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001812088	SCV000885762	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000245108	SCV000910507	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-07	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000601977	SCV001275737	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae	RCV000601977	SCV001716969	benign	Aortic aneurysm, familial thoracic 4	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000601977	SCV002014354	benign	Aortic aneurysm, familial thoracic 4	2021-09-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001775611	SCV002014355	benign	Megacystis-microcolon-intestinal hypoperistalsis syndrome 2	2021-09-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001775612	SCV002014356	benign	Visceral myopathy 2	2021-09-05	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000245108	SCV004815538	benign	Familial thoracic aortic aneurysm and aortic dissection	2024-02-05	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000146505	SCV000193795	likely benign	not specified		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000601977	SCV000733495	benign	Aortic aneurysm, familial thoracic 4		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000601977	SCV000745956	benign	Aortic aneurysm, familial thoracic 4	2014-11-19	no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000146505	SCV001952441	benign	not specified		no assertion criteria provided	clinical testing