ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.5422G>A (p.Val1808Ile) (rs780870767)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182564 SCV000234914 uncertain significance not provided 2015-05-21 criteria provided, single submitter clinical testing p.Val1808Ile (GTC>ATC): c.5422 G>A in exon 38 of the MYH11 gene (NM_002474.2). A variant of unknown significance has been identified in the MYH11 gene. The V1808I variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The V1808I variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved within mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. However, the V1808I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Missense mutations in nearby residues have not been reported, indicating this region of the protein may tolerate change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in TAAD panel(s).
Invitae RCV000685931 SCV000813432 uncertain significance Aortic aneurysm, familial thoracic 4 2018-06-01 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 1815 of the MYH11 protein (p.Val1815Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs780870767, ExAC 0.02%). This variant has not been reported in the literature in individuals with MYH11-related disease. ClinVar contains an entry for this variant (Variation ID: 201117). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Fulgent Genetics,Fulgent Genetics RCV000685931 SCV000896502 uncertain significance Aortic aneurysm, familial thoracic 4 2018-10-31 criteria provided, single submitter clinical testing
Color RCV001185747 SCV001352014 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-08-21 criteria provided, single submitter clinical testing

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