Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000420980 | SCV000519028 | likely benign | not provided | 2017-06-08 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
| Labcorp Genetics |
RCV000792626 | SCV000931932 | uncertain significance | RASopathy | 2024-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 103 of the RAF1 protein (p.His103Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with RAF1-related conditions (PMID: 20052757). ClinVar contains an entry for this variant (Variation ID: 380683). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is not expected to disrupt RAF1 function with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect RAF1 function (PMID: 20052757). 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 | RCV002323600 | SCV002608197 | uncertain significance | Cardiovascular phenotype | 2021-03-12 | criteria provided, single submitter | clinical testing | The p.H103Q variant (also known as c.309C>G), located in coding exon 2 of the RAF1 gene, results from a C to G substitution at nucleotide position 309. The histidine at codon 103 is replaced by glutamine, an amino acid with highly similar properties. This variant was reported in an individual with Noonan syndrome; however, this variant was inherited from a reportedly unaffected parent and an additional variant was also detected (Kobayashi T et al. Hum Mutat, 2010 Mar;31:284-94). This amino acid position is poorly conserved in available vertebrate species, and glutamine is the reference amino acid in other 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. |