Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001182863 | SCV001348459 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-12-04 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with alanine at codon 260 of the MYH11 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). 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 |
RCV001876077 | SCV002199274 | uncertain significance | Aortic aneurysm, familial thoracic 4 | 2023-04-15 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 260 of the MYH11 protein (p.Thr260Ala). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYH11 protein function. ClinVar contains an entry for this variant (Variation ID: 922676). |
| Ambry Genetics | RCV001182863 | SCV003855359 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-11-10 | criteria provided, single submitter | clinical testing | The p.T253A variant (also known as c.757A>G), located in coding exon 6 of the MYH11 gene, results from an A to G substitution at nucleotide position 757. The threonine at codon 253 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. 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. |
| All of Us Research Program, |
RCV001182863 | SCV005430708 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-04-17 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with alanine at codon 260 of the MYH11 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). 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. |