Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000466315 | SCV000550058 | uncertain significance | Gastrointestinal stromal tumor | 2017-05-11 | criteria provided, single submitter | clinical testing | In summary, this variant has uncertain impact on KIT function. The available evidence is currently insufficient to determine its role 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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 a KIT-related disease. ClinVar contains an entry for this variant (Variation ID: 409724). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 133 of the KIT protein (p.Leu133Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. |
Ambry Genetics | RCV004022737 | SCV005033087 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-17 | criteria provided, single submitter | clinical testing | The p.L133V variant (also known as c.397C>G), located in coding exon 3 of the KIT gene, results from a C to G substitution at nucleotide position 397. The leucine at codon 133 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |