ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.3683C>T (p.Thr1228Met)

gnomAD frequency: 0.00001  dbSNP: rs755810220
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001524888 SCV000739223 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-07-01 criteria provided, single submitter clinical testing The p.T1228M variant (also known as c.3683C>T), located in coding exon 27 of the MYH11 gene, results from a C to T substitution at nucleotide position 3683. The threonine at codon 1228 is replaced by methionine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV001524888 SCV001734859 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2020-10-05 criteria provided, single submitter clinical testing This missense variant replaces threonine with methionine at codon 1235 of the MYH11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 4/251108 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001860399 SCV002205849 uncertain significance Aortic aneurysm, familial thoracic 4 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1235 of the MYH11 protein (p.Thr1235Met). This variant is present in population databases (rs755810220, gnomAD 0.003%). 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: 519943). 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: "Possibly Damaging"; 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.
GeneDx RCV002307562 SCV002601396 uncertain significance not provided 2024-04-09 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function
All of Us Research Program, National Institutes of Health RCV001524888 SCV005430583 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-06-11 criteria provided, single submitter clinical testing This missense variant replaces threonine with methionine at codon 1235 of the MYH11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 4/251108 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.

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