Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001214763 | SCV001386466 | pathogenic | Shprintzen-Goldberg syndrome | 2021-10-11 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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 expected to disrupt SKI protein function. ClinVar contains an entry for this variant (Variation ID: 944376). This missense change has been observed in individual(s) with clinical features of Shprintzen-Goldberg syndrome (Invitae). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 89 of the SKI protein (p.Pro89Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. |