ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.5213T>C (p.Ile1738Thr)

gnomAD frequency: 0.00001  dbSNP: rs794729642
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000185544 SCV000543702 uncertain significance Aortic aneurysm, familial thoracic 4 2022-02-02 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1745 of the MYH11 protein (p.Ile1745Thr). This variant is present in population databases (rs794729642, 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: 203373). 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 disruptive. 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 RCV001804918 SCV002052220 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-05-17 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 1745 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 MYH11-related disorders in the literature. This variant has been identified in 1/260456 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.
CeGaT Center for Human Genetics Tuebingen RCV003221841 SCV003917486 uncertain significance not provided 2023-03-01 criteria provided, single submitter clinical testing MYH11: PM2, PP3
Division of Human Genetics, Children's Hospital of Philadelphia RCV000185544 SCV000238423 uncertain significance Aortic aneurysm, familial thoracic 4 2015-03-24 no assertion criteria provided research This variant (c.5234T>C) is classified as a variant of uncertain significance (VUS) because it has not previously been reported in literature and does not occur in a large database of control samples (ExAC 0.3). Computational evidence is suggestive of a pathogenic variant. It is located in highly conserved nucleotide and amino acid positions and occurs in the myosin tail functional domain according to InterPro. Furthermore, the amino acid substitution involves a change from isoleucine to threonine, which is not a conservative alteration.

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