ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1894G>A (p.Glu632Lys) (rs377767407)

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
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506202 SCV000605035 uncertain significance not specified 2017-02-14 criteria provided, single submitter clinical testing
Counsyl RCV000409907 SCV000489767 uncertain significance Multiple endocrine neoplasia, type 2b 2015-12-14 criteria provided, single submitter clinical testing
Counsyl RCV000411403 SCV000489768 uncertain significance Multiple endocrine neoplasia, type 2a 2015-12-14 criteria provided, single submitter clinical testing
GeneKor MSA RCV000708754 SCV000822192 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV000526155 SCV000658425 uncertain significance Multiple endocrine neoplasia, type 2 2018-07-12 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 632 of the RET protein (p.Glu632Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs377767407, ExAC 0.06%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in individuals affected with medullary thyroid carcinoma (PMID: 25440022, 17605401) or Hirschsprung's disease (PMID: 22648184). ClinVar contains an entry for this variant (Variation ID: 24920). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Research and Development, ARUP Laboratories RCV000506202 SCV000042484 uncertain significance not specified 2018-05-04 no assertion criteria provided literature only Single individual report: multifocal MTC at 53 yr.

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.