ClinVar Miner

Submissions for variant NM_020975.6(RET):c.340C>T (p.Arg114Cys)

gnomAD frequency: 0.00001  dbSNP: rs747483905
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000679749 SCV000807052 uncertain significance not provided 2017-12-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001218057 SCV001389924 uncertain significance Multiple endocrine neoplasia, type 2 2025-01-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 114 of the RET protein (p.Arg114Cys). This variant is present in population databases (rs747483905, gnomAD 0.007%). This missense change has been observed in individual(s) with Hirschsprung disease (PMID: 22174939). ClinVar contains an entry for this variant (Variation ID: 560870). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 RCV002458190 SCV002612748 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-06 criteria provided, single submitter clinical testing The p.R114C variant (also known as c.340C>T), located in coding exon 3 of the RET gene, results from a C to T substitution at nucleotide position 340. The arginine at codon 114 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in individuals affected with Hirschsprung disease (So MT et al. PLoS One, 2011 Dec;6:e28986; Tang CS et al. Gastroenterology, 2018 12;155:1908-1922.e5). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV001218057 SCV004834379 uncertain significance Multiple endocrine neoplasia, type 2 2024-01-03 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005034286 SCV005666814 uncertain significance Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A 2024-03-12 criteria provided, single submitter clinical testing

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.