Submissions for variant NM_002474.3(MYH11):c.4673C>T (p.Thr1558Met)

gnomAD frequency: 0.00078  dbSNP: rs111854563

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000588245	SCV000234910	likely benign	not provided	2020-09-25	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23142374, 26017485, 27647783)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001082621	SCV000556092	likely benign	Aortic aneurysm, familial thoracic 4	2024-01-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588245	SCV000697648	benign	not provided	2016-02-22	criteria provided, single submitter	clinical testing	Variant summary: This c.4694C>T variant affects a conserved nucleotide, resulting in amino acid change from Thr to Met. 3/4 in-silico tools predict this variant to be damaging; however they are not definite. This variant was found in 94/122406 control chromosomes at a frequency of 0.0007679, which is more than 613 times greater than the maximal expected frequency of a pathogenic allele (0.0000013) in this gene, suggesting this variant is benign. At least one clinical lab has classified this variant as likely benign. Taken together, this variant has been classified as Benign.
Ambry Genetics	RCV000157333	SCV000739212	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-05-08	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.
CeGaT Center for Human Genetics Tuebingen	RCV000588245	SCV001249512	likely benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	MYH11: PP3, BS1
Illumina Laboratory Services, Illumina	RCV001082621	SCV001277601	benign	Aortic aneurysm, familial thoracic 4	2017-09-14	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000157333	SCV001333420	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-10-30	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000157333	SCV001344866	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-10-24	criteria provided, single submitter	clinical testing
Department of Vascular Biology, Beijing Anzhen Hospital	RCV001374830	SCV001439579	uncertain significance	Isolated thoracic aortic aneurysm	2018-09-01	criteria provided, single submitter	research
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588245	SCV004562768	likely benign	not provided	2023-05-02	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV000157333	SCV000207070	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2014-11-03	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003927518	SCV004746586	likely benign	MYH11-related disorder	2022-12-21	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).