ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.5787-4707C>T (rs111588143)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182566 SCV000234916 uncertain significance not provided 2018-11-07 criteria provided, single submitter clinical testing p.Pro1933Leu (CCA>CTA): c.5798 C>T in exon 41 of the MYH11 gene (#NM_022844.2). A variant of unknown significance has been identified in an alternate transcript of the MYH11 gene. The P1933L variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The P1933L 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 P1933L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved across species. 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 this transcript have not been reported in association with TAAD. 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).
Color RCV000778048 SCV000914162 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2020-01-28 criteria provided, single submitter clinical testing
Invitae RCV001069934 SCV001235132 uncertain significance Aortic aneurysm, familial thoracic 4 2019-11-25 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1940 of the MYH11 protein (p.Pro1940Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs111588143, ExAC 0.004%). This variant has not been reported in the literature in individuals with MYH11-related conditions. ClinVar contains an entry for this variant (Variation ID: 201119). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.

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