Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001059783 | SCV001224430 | uncertain significance | Shprintzen-Goldberg syndrome | 2022-05-25 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 854684). This variant has not been reported in the literature in individuals affected with SKI-related conditions. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 585 of the SKI protein (p.Arg585His). |
| Gene |
RCV001760017 | SCV001991850 | uncertain significance | not provided | 2019-04-08 | 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 that this variant does not alter protein structure/function; Not observed in large population cohorts (Lek et al., 2016) |
| Ambry Genetics | RCV002402429 | SCV002714311 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-05-16 | criteria provided, single submitter | clinical testing | The p.R585H variant (also known as c.1754G>A), located in coding exon 5 of the SKI gene, results from a G to A substitution at nucleotide position 1754. The arginine at codon 585 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV001059783 | SCV003806774 | uncertain significance | Shprintzen-Goldberg syndrome | 2022-08-19 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PM2 moderated |