Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000419670 | SCV000814521 | uncertain significance | Gastrointestinal stromal tumor | 2018-06-01 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with lysine at codon 822 of the KIT protein (p.Asn822Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported as a germline variant in the literature in individuals with KIT-related disease. ClinVar contains an entry for this variant (Variation ID: 375931). Experimental studies have shown that this missense change results in constitutive phosphorylation of the KIT protein, increased cell proliferation in the presence of low concentration of growth factors, impaired apoptosis promotion, and resistance to low doses of imatinib (PMID: 14645423, 14695343, 17699867, 20890793, 28506695). 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. |
Clinical Genetics and Genomics, |
RCV001269701 | SCV001449892 | pathogenic | not provided | 2017-03-07 | criteria provided, single submitter | clinical testing | |
Database of Curated Mutations |
RCV000419670 | SCV000504217 | likely pathogenic | Gastrointestinal stromal tumor | 2015-07-14 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000429954 | SCV000504218 | likely pathogenic | Acute myeloid leukemia | 2014-12-26 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000436687 | SCV000504219 | pathogenic | Melanoma | 2014-10-02 | no assertion criteria provided | literature only |