Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002234321 | SCV000938069 | uncertain significance | HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with leucine at codon 23 of the CBS protein (p.Ser23Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs775785018, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with CBS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Gene |
RCV001538815 | SCV001756518 | uncertain significance | not provided | 2020-06-19 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV003166168 | SCV003861112 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2023-02-20 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Natera, |
RCV000798452 | SCV001460092 | uncertain significance | Classic homocystinuria | 2020-01-17 | no assertion criteria provided | clinical testing |