Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001063359 | SCV001228200 | uncertain significance | Gastrointestinal stromal tumor | 2023-01-26 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). ClinVar contains an entry for this variant (Variation ID: 857642). This variant has not been reported in the literature in individuals affected with KIT-related conditions. 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 855 of the KIT protein (p.Tyr855Cys). |
Gene |
RCV002255175 | SCV002526476 | likely pathogenic | not provided | 2022-09-02 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002429705 | SCV002741192 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-16 | criteria provided, single submitter | clinical testing | The p.Y855C variant (also known as c.2564A>G), located in coding exon 18 of the KIT gene, results from an A to G substitution at nucleotide position 2564. The tyrosine at codon 855 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |
Center for Genomics, |
RCV003224519 | SCV003920114 | uncertain significance | Gastrointestinal stromal tumor; Piebaldism; Acute myeloid leukemia; Cutaneous mastocytosis; Germ cell tumor of testis | 2022-08-04 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature and is not present in large control databases. This variant is present in ClinVar (Variation ID:857642). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |