Submissions for variant NM_001040113.2(MYH11):c.5819C>A (p.Pro1940Gln)

dbSNP: rs111588143

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000249091	SCV000234827	benign	not specified	2015-06-25	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	RCV000234725	SCV000285802	benign	Aortic aneurysm, familial thoracic 4	2025-01-29	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000249091	SCV000306213	benign	not specified		criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770686	SCV000902153	benign	Familial thoracic aortic aneurysm and aortic dissection	2019-05-10	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000770686	SCV000911002	likely 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	RCV000249091	SCV000919822	benign	not specified	2018-12-11	criteria provided, single submitter	clinical testing	Variant summary: MYH11 c.5819C>A (p.Pro1940Gln) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0015 in 259712 control chromosomes in the gnomAD database, including 1 homozygote. The observed variant frequency is approximately 1229-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in MYH11 causing Aortopathy phenotype (1.3e-06), strongly suggesting that the variant is benign. Yeung_2017 reports the variant in one patient with aortic aneurysm (AA) and following an evaluation of the effect of the variant on RNA splicing concluded that transcripts containing exon 42 are not expressed in smooth muscle cell (SMC)-like cells or primary SMC and therefore, the variant c.5819C>A in MYH11 is not pathogenic and variants in exon 42 are not relevant for familial thoracic AA. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant twice as benign and once as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001579871	SCV003799676	likely benign	not provided	2023-11-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001579871	SCV004010459	likely benign	not provided	2024-09-01	criteria provided, single submitter	clinical testing	MYH11: BP4, BS2; NDE1: BS2
Breakthrough Genomics, Breakthrough Genomics	RCV001579871	SCV005217507	likely benign	not provided		criteria provided, single submitter	not provided
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV000234725	SCV000493769	uncertain significance	Aortic aneurysm, familial thoracic 4	2016-03-30	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001579871	SCV001808793	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000249091	SCV001929535	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001579871	SCV001964787	likely benign	not provided		no assertion criteria provided	clinical testing