Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002455166 | SCV002617371 | uncertain significance | Cardiovascular phenotype | 2022-01-28 | criteria provided, single submitter | clinical testing | The p.R120Q variant (also known as c.359G>A), located in coding exon 4 of the RIT1 gene, results from a G to A substitution at nucleotide position 359. The arginine at codon 120 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003099606 | SCV003460368 | uncertain significance | Noonan syndrome 8 | 2024-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 120 of the RIT1 protein (p.Arg120Gln). This variant is present in population databases (rs753425443, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with RIT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1733049). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt RIT1 protein function with a negative predictive value of 95%. 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. |
Genome- |
RCV003099606 | SCV004050456 | uncertain significance | Noonan syndrome 8 | 2023-04-11 | criteria provided, single submitter | clinical testing |