Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001010374 | SCV001170562 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-13 | criteria provided, single submitter | clinical testing | The p.N406S variant (also known as c.1217A>G), located in coding exon 7 of the KIT gene, results from an A to G substitution at nucleotide position 1217. The asparagine at codon 406 is replaced by serine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001862767 | SCV002145240 | uncertain significance | Gastrointestinal stromal tumor | 2022-09-27 | 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: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 818616). This variant has not been reported in the literature in individuals affected with KIT-related conditions. This variant is present in population databases (rs771574892, gnomAD 0.0009%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 406 of the KIT protein (p.Asn406Ser). |