Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001044986 | SCV001208813 | uncertain significance | RASopathy | 2019-03-22 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with RAF1-related conditions. This sequence change replaces arginine with leucine at codon 333 of the RAF1 protein (p.Arg333Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
Prevention |
RCV004738129 | SCV005344388 | uncertain significance | RAF1-related disorder | 2024-03-22 | no assertion criteria provided | clinical testing | The RAF1 c.998G>T variant is predicted to result in the amino acid substitution p.Arg333Leu. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |