Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004118768 | SCV003603606 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-12-07 | criteria provided, single submitter | clinical testing | The c.637C>T (p.L213F) alteration is located in exon 1 (coding exon 1) of the SKI gene. This alteration results from a C to T substitution at nucleotide position 637, causing the leucine (L) at amino acid position 213 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003631280 | SCV004530339 | uncertain significance | Shprintzen-Goldberg syndrome | 2023-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 213 of the SKI protein (p.Leu213Phe). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with SKI-related conditions. ClinVar contains an entry for this variant (Variation ID: 2266305). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SKI 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. |