Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000213202 | SCV000272345 | uncertain significance | not specified | 2015-05-18 | criteria provided, single submitter | clinical testing | The p.Asn140Ser variant in RAF1 has not been previously reported in individuals with clinical features of Noonan syndrome or in large population studies. Comput ational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Asn140Ser variant is uncertain. |
| Ambry Genetics | RCV000621025 | SCV000740120 | uncertain significance | Cardiovascular phenotype | 2021-04-14 | criteria provided, single submitter | clinical testing | The p.N140S variant (also known as c.419A>G), located in coding exon 3 of the RAF1 gene, results from an A to G substitution at nucleotide position 419. The asparagine at codon 140 is replaced by serine, 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. |
| Labcorp Genetics |
RCV001233366 | SCV001405956 | uncertain significance | RASopathy | 2023-09-06 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 229179). This variant has not been reported in the literature in individuals affected with RAF1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 140 of the RAF1 protein (p.Asn140Ser). 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. |
| Mayo Clinic Laboratories, |
RCV002261011 | SCV002542027 | uncertain significance | not provided | 2022-01-11 | criteria provided, single submitter | clinical testing |