ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2080C>T (p.Arg694Trp) (rs193922700)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000770758 SCV000053075 uncertain significance not specified 2019-02-20 criteria provided, single submitter clinical testing Variant summary: RET c.2080C>T (p.Arg694Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 275790 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2080C>T has been reported in the literature in an individual affected with breast cancer (Sun_2017). This report does not provide unequivocal conclusions about association of the variant with Multiple Endocrine Neoplasia Type 2. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Counsyl RCV000030406 SCV000786028 uncertain significance Multiple endocrine neoplasia, type 2a 2018-02-06 criteria provided, single submitter clinical testing
GeneKor MSA RCV000708755 SCV000822194 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV000698016 SCV000826654 uncertain significance Multiple endocrine neoplasia, type 2 2019-06-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 694 of the RET protein (p.Arg694Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with breast cancer (PMID: 28724667). ClinVar contains an entry for this variant (Variation ID: 36727). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.