ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2876G>A (p.Arg959Gln) (rs745650861)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000406955 SCV000362372 uncertain significance Multiple endocrine neoplasia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000303500 SCV000362373 uncertain significance Renal adysplasia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000358250 SCV000362374 uncertain significance Pheochromocytoma 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000268422 SCV000362375 uncertain significance Hirschsprung Disease, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000568661 SCV000674896 uncertain significance Hereditary cancer-predisposing syndrome 2016-06-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000654551 SCV000776445 uncertain significance Multiple endocrine neoplasia, type 2 2017-11-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 959 of the RET protein (p.Arg959Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs745650861, ExAC 0.02%). This variant has not been reported in the literature in individuals with RET-related disease. ClinVar contains an entry for this variant (Variation ID: 299901). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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.