Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001563672 | SCV001786661 | uncertain significance | Noonan syndrome 9 | 2021-03-04 | criteria provided, single submitter | clinical testing | The SOS2 c.530A>G (p.Asp177Gly) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. The p.Asp177Gly variant is reported at a frequency of 0.000009 in the European (non-Finnish) population in the Genome Aggregation Database, but this is based on one allele in a region of good sequence coverage, so the variant is presumed to be rare. Based on the limited evidence, the p.Asp177Gly variant is classified as a variant of uncertain significance for Noonan syndrome. |
Labcorp Genetics |
RCV001563672 | SCV003467413 | uncertain significance | Noonan syndrome 9 | 2022-03-11 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 177 of the SOS2 protein (p.Asp177Gly). This variant is present in population databases (no rsID available, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SOS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 981588). 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 not expected to disrupt SOS2 protein function. 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. |
Service de Génétique Moléculaire, |
RCV001261118 | SCV001438525 | uncertain significance | Noonan syndrome | no assertion criteria provided | clinical testing |