ClinVar Miner

Submissions for variant NM_000222.3(KIT):c.1675G>A (p.Val559Ile)

dbSNP: rs121913520
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Total submissions: 3
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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 (DoCM) RCV000426761 SCV000504986 likely pathogenic Myeloproliferative neoplasm 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436995 SCV000504987 likely pathogenic Gastrointestinal stromal tumor 2014-12-26 no assertion criteria provided literature only

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