Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001944576 | SCV002131149 | uncertain significance | Gastrointestinal stromal tumor | 2021-08-30 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with piebaldism (PMID: 16220461). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with isoleucine at codon 604 of the KIT protein (p.Val604Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |