Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002971900 | SCV003284873 | uncertain significance | Gastrointestinal stromal tumor | 2022-08-16 | 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on KIT function (PMID: 23567324). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with gastrointestinal stromal tumor samples (PMID: 23567324, 25886408). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 578 of the KIT protein (p.Tyr578Cys). |
| Ambry Genetics | RCV003377821 | SCV004098441 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-02 | criteria provided, single submitter | clinical testing | The p.Y578C variant (also known as c.1733A>G), located in coding exon 11 of the KIT gene, results from an A to G substitution at nucleotide position 1733. The tyrosine at codon 578 is replaced by cysteine, an amino acid with highly dissimilar 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |