Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001041017 | SCV001204611 | uncertain significance | Aortic aneurysm, familial thoracic 4 | 2024-02-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 936 of the MYH11 protein (p.Ala936Ser). This variant is present in population databases (no rsID available, gnomAD 0.02%). 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: 839295). 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 with a negative predictive value of 95%. 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. |
| Ambry Genetics | RCV002436550 | SCV002748271 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-03-22 | criteria provided, single submitter | clinical testing | The p.A929S variant (also known as c.2785G>T), located in coding exon 21 of the MYH11 gene, results from a G to T substitution at nucleotide position 2785. The alanine at codon 929 is replaced by serine, 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. |
| Fulgent Genetics, |
RCV002505568 | SCV002814512 | uncertain significance | Aortic aneurysm, familial thoracic 4; Visceral myopathy 2; Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 | 2021-08-20 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003323784 | SCV004028855 | uncertain significance | not specified | 2023-07-21 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV002436550 | SCV004819932 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-09-23 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with serine at codon 936 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 MYH11-related disorders in the literature. This variant has been identified in 4/280178 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. |