Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001876392 | SCV002125459 | uncertain significance | Noonan syndrome 9 | 2021-05-18 | criteria provided, single submitter | clinical testing | 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"). 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 variant has not been reported in the literature in individuals with SOS2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with isoleucine at codon 337 of the SOS2 protein (p.Leu337Ile). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and isoleucine. |
| Ambry Genetics | RCV004671461 | SCV005170324 | uncertain significance | Cardiovascular phenotype | 2024-05-05 | criteria provided, single submitter | clinical testing | The p.L337I variant (also known as c.1009C>A), located in coding exon 8 of the SOS2 gene, results from a C to A substitution at nucleotide position 1009. The leucine at codon 337 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |