Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Blueprint Genetics | RCV000208423 | SCV000264225 | likely benign | not specified | 2015-07-01 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000701953 | SCV000830779 | uncertain significance | Shprintzen-Goldberg syndrome | 2018-07-08 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with serine at codon 361 of the SKI protein (p.Gly361Ser). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and serine. This variant has not been reported in the literature in individuals with SKI-related disease. ClinVar contains an entry for this variant (Variation ID: 222820). This variant is present in population databases (rs759663808, ExAC 0.01%). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. |
| Ambry Genetics | RCV002426979 | SCV002730278 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2020-11-03 | 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. |