Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000475694 | SCV000550383 | uncertain significance | Shprintzen-Goldberg syndrome | 2016-09-23 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change with uncertain impact on protein function. While it is absent from the population and affects an important residue, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Two different missense substitutions at this codon (p.Pro35Ser and p.Pro35Gln) have been determined to be pathogenic (PMID: 23023332, 23103230). This suggests that the proline residue is critical for SKI protein function and that other missense substitutions at this position may also be pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a SKI-related disease. This sequence change replaces proline with arginine at codon 35 of the SKI protein (p.Pro35Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine. |
| Genetic Services Laboratory, |
RCV000475694 | SCV000597058 | likely pathogenic | Shprintzen-Goldberg syndrome | 2016-09-21 | criteria provided, single submitter | clinical testing | |
| Kasturba Medical College, |
RCV000475694 | SCV002053865 | likely pathogenic | Shprintzen-Goldberg syndrome | criteria provided, single submitter | research |