Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000182522 | SCV000234869 | uncertain significance | not provided | 2017-06-14 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the MYH11 gene. The K1573E variant has been reported in one patient with sudden unexplained death who also harbored other potentially disease-causing variants (Hata et al., 2017). This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The K1573E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, this variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity. |
| Color Diagnostics, |
RCV001186508 | SCV001352957 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-01-26 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with glutamic acid at codon 1580 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 been reported in an individual affected with sudden unexpected death (PMID: 28469501). This variant has been identified in 9/282854 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. |
| Fulgent Genetics, |
RCV002478617 | SCV002783019 | uncertain significance | Aortic aneurysm, familial thoracic 4; Visceral myopathy 2; Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 | 2021-11-05 | criteria provided, single submitter | clinical testing |