Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001204194 | SCV001375390 | uncertain significance | Gastrointestinal stromal tumor | 2021-04-06 | 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. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with KIT-related conditions. This variant is present in population databases (rs144369407, ExAC 0.001%). This sequence change replaces arginine with glycine at codon 634 of the KIT protein (p.Arg634Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. |
| Ambry Genetics | RCV003294000 | SCV004000285 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-24 | criteria provided, single submitter | clinical testing | The p.R634G variant (also known as c.1900C>G), located in coding exon 13 of the KIT gene, results from a C to G substitution at nucleotide position 1900. The arginine at codon 634 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available 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. |