ClinVar Miner

Submissions for variant NM_000222.3(KIT):c.1331C>T (p.Pro444Leu)

dbSNP: rs774389709
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002024454 SCV002315919 uncertain significance Gastrointestinal stromal tumor 2021-09-24 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 444 of the KIT protein (p.Pro444Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs774389709, ExAC 0.001%). This variant has not been reported in the literature in individuals with KIT-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine 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. 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 RCV002386930 SCV002692596 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-22 criteria provided, single submitter clinical testing The p.P444L variant (also known as c.1331C>T), located in coding exon 8 of the KIT gene, results from a C to T substitution at nucleotide position 1331. The proline at codon 444 is replaced by leucine, an amino acid with similar 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.
Baylor Genetics RCV002024454 SCV004190372 uncertain significance Gastrointestinal stromal tumor 2023-07-11 criteria provided, single submitter clinical testing

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