Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000247569 | SCV000319368 | uncertain significance | Cardiovascular phenotype | 2014-11-25 | criteria provided, single submitter | clinical testing | There is insufficient or conflicting evidence for classification of this alteration. |
Invitae | RCV000553332 | SCV000641075 | uncertain significance | Aortic aneurysm, familial thoracic 4 | 2023-05-10 | criteria provided, single submitter | clinical testing | 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: 263884). This variant is present in population databases (rs148743922, gnomAD 0.03%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1873 of the MYH11 protein (p.Glu1873Lys). |
Color Diagnostics, |
RCV000777865 | SCV000913871 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-11-03 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with lysine at codon 1873 of the MYH11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 cardiovascular disorders in the literature. This variant has been identified in 11/282646 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. |
Gene |
RCV001753734 | SCV002005181 | uncertain significance | not provided | 2019-09-30 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID# 263884; Landrum et al., 2016) |