Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193136 | SCV001361779 | uncertain significance | not specified | 2019-05-13 | criteria provided, single submitter | clinical testing | Variant summary: RAF1 c.1910G>A (p.Cys637Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251302 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1910G>A in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV002411726 | SCV002717944 | uncertain significance | Cardiovascular phenotype | 2022-06-14 | criteria provided, single submitter | clinical testing | The p.C637Y variant (also known as c.1910G>A), located in coding exon 16 of the RAF1 gene, results from a G to A substitution at nucleotide position 1910. The cysteine at codon 637 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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 |
RCV002560161 | SCV003446255 | uncertain significance | RASopathy | 2023-09-05 | criteria provided, single submitter | clinical testing | 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RAF1 protein function. ClinVar contains an entry for this variant (Variation ID: 928753). This missense change has been observed in individual(s) with clinical features of RAF-related conditions (PMID: 35418823). This variant is present in population databases (rs769639669, gnomAD 0.004%). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 637 of the RAF1 protein (p.Cys637Tyr). |