Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000436995 | SCV001509254 | uncertain significance | Gastrointestinal stromal tumor | 2022-12-31 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 376056). This variant has not been reported in the literature in individuals affected with KIT-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 559 of the KIT protein (p.Val559Ile). 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. 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. This variant disrupts the p.Val559 amino acid residue in KIT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11208730, 11505412, 15837988, 24847623). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects KIT function (PMID: 17259998). |
| Database of Curated Mutations |
RCV000426761 | SCV000504986 | likely pathogenic | Myeloproliferative neoplasm | 2015-07-14 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000436995 | SCV000504987 | likely pathogenic | Gastrointestinal stromal tumor | 2014-12-26 | no assertion criteria provided | literature only |