ClinVar Miner

Submissions for variant NM_000222.3(KIT):c.2858A>G (p.His953Arg)

gnomAD frequency: 0.00001  dbSNP: rs1723056214
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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 RCV001360634 SCV001556561 uncertain significance Gastrointestinal stromal tumor 2021-10-02 criteria provided, single submitter clinical testing 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. 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 C25". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with KIT-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with arginine at codon 953 of the KIT protein (p.His953Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine.
GeneDx RCV004590350 SCV005079295 uncertain significance not provided 2023-12-14 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 RCV004951604 SCV005608778 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-15 criteria provided, single submitter clinical testing The p.H953R variant (also known as c.2858A>G), located in coding exon 21 of the KIT gene, results from an A to G substitution at nucleotide position 2858. The histidine at codon 953 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. 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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