Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000813097 | SCV000953435 | uncertain significance | Gastrointestinal stromal tumor | 2018-09-24 | 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 proline amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with KIT-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with proline at codon 389 of the KIT protein (p.Thr389Pro). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and proline. |
Ambry Genetics | RCV002325590 | SCV002627117 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-08-12 | criteria provided, single submitter | clinical testing | The p.T389P variant (also known as c.1165A>C), located in coding exon 7 of the KIT gene, results from an A to C substitution at nucleotide position 1165. The threonine at codon 389 is replaced by proline, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |