Submissions for variant NM_002474.3(MYH11):c.267C>A (p.Asp89Glu)

dbSNP: rs775840903

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001805509	SCV002053099	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2022-12-21	criteria provided, single submitter	clinical testing	This missense variant replaces aspartic acid with glutamic acid at codon 89 of the MYH11 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/251486 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV001805509	SCV002744685	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-09-08	criteria provided, single submitter	clinical testing	The p.D89E variant (also known as c.267C>A), located in coding exon 1 of the MYH11 gene, results from a C to A substitution at nucleotide position 267. The aspartic acid at codon 89 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002541435	SCV003510098	uncertain significance	Aortic aneurysm, familial thoracic 4	2024-07-16	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 89 of the MYH11 protein (p.Asp89Glu). This variant is present in population databases (rs775840903, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. ClinVar contains an entry for this variant (Variation ID: 1332463). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MYH11 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health	RCV001805509	SCV004816883	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2024-07-20	criteria provided, single submitter	clinical testing	This missense variant replaces aspartic acid with glutamic acid at codon 89 of the MYH11 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/251486 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.