ClinVar Miner

Submissions for variant NM_000222.3(KIT):c.2554G>A (p.Val852Ile)

gnomAD frequency: 0.00002  dbSNP: rs555650901
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000470685 SCV000550076 uncertain significance Gastrointestinal stromal tumor 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 852 of the KIT protein (p.Val852Ile). This variant is present in population databases (rs555650901, gnomAD 0.004%). 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: 134625). 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 RCV001015943 SCV001176838 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-08 criteria provided, single submitter clinical testing The p.V852I variant (also known as c.2554G>A), located in coding exon 18 of the KIT gene, results from a G to A substitution at nucleotide position 2554. The valine at codon 852 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV002274916 SCV002562371 uncertain significance not provided 2024-07-05 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Observed in an individual from a high-risk colorectal cancer family (PMID: 30256826); This variant is associated with the following publications: (PMID: 24728327, 30256826)
ITMI RCV000121318 SCV000085489 not provided not specified 2013-09-19 no assertion provided reference population
PreventionGenetics, part of Exact Sciences RCV003894963 SCV004713844 uncertain significance KIT-related disorder 2024-01-18 no assertion criteria provided clinical testing The KIT c.2554G>A variant is predicted to result in the amino acid substitution p.Val852Ile. This variant has been reported in a healthy, ancestrally diverse genome sequencing cohort (Table S1, Bodian et al. 2014. PubMed ID: 24728327). This variant is reported in 0.0035% of alleles in individuals of European (Non-Finnish) descent in gnomAD. It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/134625/). 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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