Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001040008 | SCV001203560 | uncertain significance | Gastrointestinal stromal tumor | 2023-12-26 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 899 of the KIT protein (p.Met899Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KIT-related conditions. ClinVar contains an entry for this variant (Variation ID: 838460). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV002434451 | SCV002745354 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-27 | criteria provided, single submitter | clinical testing | The p.M899I variant (also known as c.2697G>T) is located in coding exon 20 of the KIT gene. The methionine at codon 899 is replaced by isoleucine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 20. 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. |