ClinVar Miner

Submissions for variant NM_000222.3(KIT):c.65C>T (p.Thr22Ile)

gnomAD frequency: 0.00001  dbSNP: rs769943127
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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 RCV000814947 SCV000955385 uncertain significance Gastrointestinal stromal tumor 2024-06-21 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 22 of the KIT protein (p.Thr22Ile). This variant is present in population databases (rs769943127, gnomAD 0.002%). 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: 658178). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
GeneDx RCV003318644 SCV004023015 uncertain significance not provided 2023-07-23 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV005367584 SCV006023549 uncertain significance Hereditary cancer-predisposing syndrome 2024-12-12 criteria provided, single submitter clinical testing The p.T22I variant (also known as c.65C>T), located in coding exon 1 of the KIT gene, results from a C to T substitution at nucleotide position 65. The threonine at codon 22 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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