ClinVar Miner

Submissions for variant NM_000222.3(KIT):c.1656G>A (p.Met552Ile)

gnomAD frequency: 0.00001  dbSNP: rs1482011071
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001208702 SCV001380106 uncertain significance Gastrointestinal stromal tumor 2023-10-04 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 552 of the KIT protein (p.Met552Ile). 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: 939321). 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. 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.
Sema4, Sema4 RCV002259090 SCV002536388 uncertain significance Hereditary cancer-predisposing syndrome 2021-07-08 criteria provided, single submitter curation
Ambry Genetics RCV002259090 SCV005033060 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-15 criteria provided, single submitter clinical testing The p.M552I variant (also known as c.1656G>A), located in coding exon 11 of the KIT gene, results from a G to A substitution at nucleotide position 1656. The methionine at codon 552 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003898200 SCV004711842 uncertain significance KIT-related disorder 2023-12-26 no assertion criteria provided clinical testing The KIT c.1656G>A variant is predicted to result in the amino acid substitution p.Met552Ile. To our knowledge, this variant has not been reported in the literature in individuals with inherited KIT-related conditions. It has not been reported in a large population database, indicating this variant is rare. It is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/939321/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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