ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.5371G>A (p.Glu1791Lys)

dbSNP: rs368269107
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230804 SCV000285801 uncertain significance Aortic aneurysm, familial thoracic 4 2024-01-28 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1798 of the MYH11 protein (p.Glu1798Lys). This variant is present in population databases (rs368269107, gnomAD 0.004%). 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: 238262). 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) performed at Invitae indicates that this missense variant is not expected to disrupt MYH11 protein function with a negative predictive value of 95%. 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.
Color Diagnostics, LLC DBA Color Health RCV001184025 SCV001349896 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-03-21 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 1798 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 5/251070 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.
GeneDx RCV001753691 SCV002007232 uncertain significance not provided 2022-08-09 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV001184025 SCV003912527 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-02-16 criteria provided, single submitter clinical testing The p.E1791K variant (also known as c.5371G>A), located in coding exon 37 of the MYH11 gene, results from a G to A substitution at nucleotide position 5371. The glutamic acid at codon 1791 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. 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.

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