ClinVar Miner

Submissions for variant NM_000222.3(KIT):c.2273A>G (p.Glu758Gly)

gnomAD frequency: 0.00001  dbSNP: rs749166896
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000633719 SCV000754992 uncertain significance Gastrointestinal stromal tumor 2021-08-26 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 758 of the KIT protein (p.Glu758Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (rs749166896, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with KIT-related conditions. 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. 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.
Ambry Genetics RCV001014861 SCV001175626 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-24 criteria provided, single submitter clinical testing The p.E758G variant (also known as c.2273A>G), located in coding exon 16 of the KIT gene, results from an A to G substitution at nucleotide position 2273. The glutamic acid at codon 758 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.