Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001752623 | SCV001997528 | uncertain significance | not provided | 2020-01-03 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function |
Ambry Genetics | RCV002425053 | SCV002741023 | uncertain significance | Cardiovascular phenotype | 2021-04-05 | criteria provided, single submitter | clinical testing | The p.L831V variant (also known as c.2491C>G), located in coding exon 15 of the SOS1 gene, results from a C to G substitution at nucleotide position 2491. The leucine at codon 831 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
Genome- |
RCV002468305 | SCV002763297 | uncertain significance | Noonan syndrome 4 | criteria provided, single submitter | clinical testing | ||
Genome- |
RCV002468304 | SCV002763298 | uncertain significance | Fibromatosis, gingival, 1 | criteria provided, single submitter | clinical testing | ||
Labcorp Genetics |
RCV003539404 | SCV004274277 | uncertain significance | RASopathy | 2023-01-07 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1311640). This variant has not been reported in the literature in individuals affected with SOS1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 831 of the SOS1 protein (p.Leu831Val). |