Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001940388 | SCV002189602 | uncertain significance | RASopathy | 2022-08-21 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1418266). This variant has not been reported in the literature in individuals affected with RAF1-related conditions. This variant is present in population databases (rs140884322, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 73 of the RAF1 protein (p.Arg73Gln). 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 expected to disrupt RAF1 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. |
| Ambry Genetics | RCV002425247 | SCV002728625 | uncertain significance | Cardiovascular phenotype | 2021-03-29 | criteria provided, single submitter | clinical testing | The p.R73Q variant (also known as c.218G>A), located in coding exon 2 of the RAF1 gene, results from a G to A substitution at nucleotide position 218. The arginine at codon 73 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |