ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.3932C>T (p.Ala1311Val) (rs185720909)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182513 SCV000234859 uncertain significance not provided 2016-12-21 criteria provided, single submitter clinical testing p.Ala1311Val (GCG>GTG): c.3932 C>T in exon 29 of the MYH11 gene (NM_002474.2)A variant of unknown significance has been identified in the MYH11 gene. The A1311V variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The A1311V 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. The A1311V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that conserved among mammals and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, missense mutations in nearby residues have not been reported, indicating this region of the protein may be tolerant of 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 RCV000822715 SCV000963529 uncertain significance Aortic aneurysm, familial thoracic 4 2018-08-28 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 1318 of the MYH11 protein (p.Ala1318Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs185720909, ExAC 0.03%). This variant has not been reported in the literature in individuals with MYH11-related disease. ClinVar contains an entry for this variant (Variation ID: 201069). 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.
Color RCV001184502 SCV001350481 likely benign Familial thoracic aortic aneurysm and aortic dissection 2019-09-24 criteria provided, single submitter clinical testing

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