ClinVar Miner

Submissions for variant NM_000222.3(KIT):c.2732C>A (p.Pro911His)

dbSNP: rs772159767
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000556945 SCV000630481 uncertain significance Gastrointestinal stromal tumor 2023-08-17 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 911 of the KIT protein (p.Pro911His). This variant is present in population databases (rs772159767, gnomAD 0.02%). 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: 458929). 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 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.
Ambry Genetics RCV004948398 SCV005608766 uncertain significance Hereditary cancer-predisposing syndrome 2024-08-20 criteria provided, single submitter clinical testing The p.P911H variant (also known as c.2732C>A), located in coding exon 20 of the KIT gene, results from a C to A substitution at nucleotide position 2732. The proline at codon 911 is replaced by histidine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on data from gnomAD, the frequency for this variant is above the maximum credible frequency for a disease-causing variant in this gene based on internally established thresholds (Karczewski et al. Nature. 2020 May;581(7809):434-443; Whiffin et al. Genet Med. 2017 10;19:1151-1158). Based on the available evidence, the clinical significance of this variant remains unclear.

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