Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetics and Molecular Pathology, |
RCV002272619 | SCV002556485 | uncertain significance | Noonan syndrome 4 | 2020-04-03 | criteria provided, single submitter | clinical testing | The SOS1 c.2764A>G variant is a single nucleotide change from an adenine to a guanine at position 2764 which is predicted to change the isoleucine at position 922 in the protein to valine. The variant has not been described in the literature to date. The variant is in dbSNP (rs780420674) and has been reported once in population databases (gnomAD 1/250838, 0 homozygotes) (PM2). The variant has not been reported in the ClinVar or HGMD disease databases. Computational predictions are conflicting: the residue is conserved but in silico tools predict a benign effect (neither BP4 or PP3 applied). |
| Invitae | RCV003096130 | SCV002986893 | uncertain significance | RASopathy | 2022-05-12 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 922 of the SOS1 protein (p.Ile922Val). This variant is present in population databases (rs780420674, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SOS1-related conditions. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). |