ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1858T>G (p.Cys620Gly) (rs77316810)

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
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000507202 SCV000605030 pathogenic not specified 2016-11-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV000575015 SCV000664450 pathogenic Hereditary cancer-predisposing syndrome 2018-09-13 criteria provided, single submitter clinical testing Well-characterized mutation at same position;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Other strong data supporting pathogenic classification;Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Moderate segregation with disease (at least 3 informative meioses) for rare diseases.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000824755 SCV000711448 pathogenic Multiple endocrine neoplasia, type 2; Hirschsprung disease 2017-07-24 criteria provided, single submitter clinical testing The p.Cys620Gly variant in RET has been reported in at least 10 probands with R ET-associated disorders (diagnoses included medullary thyroid carcinoma (MTC), m ultiple endocrine neoplasia type 2A (MEN2A), and/or Hirschsprung disease) and se gregated with disease in at least 4 individuals from at least family (Kitamura 1 997, Niccoli-Sire 2001, Kruckeberg 2004, Frank-Raue 2011). This variant has also been reported by other clinical laboratories in ClinVar (Variation ID# 24905) a nd was absent from large population studies. Additionally, other amino acid cha nges at this position have been reported in patients with MEN2A, and variants at cysteine residues in exon 10 or 11 of RET account for the majority of familial MTC and MEN2A cases (Hansford 2000, Kruckeberg 2004, Coyle 2014). Computational prediction tools and conservation analysis also suggest that the p.Cys620Gly var iant may impact the protein. In summary, this variant meets criteria to be class ified as pathogenic for MEN2A in an autosomal dominant manner based on presence in multiple affected individuals, segregation studies, absence from the general population, presence in a mutational hotspot and computational evidence. ACMG/AM P Criteria applied: PS4, PM1, PM2, PP3, PP1_supporting (Richards 2015).
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV000709757 SCV000840055 pathogenic Multiple endocrine neoplasia, type 2a 2018-04-10 criteria provided, single submitter clinical testing This c.1858T>G (p.Cys620Gly) variant in the RET gene has been reported in multiple unrelated individuals with medullary thyroid carcinoma and Hurschsprung disease (PMID: 8918855, 9223675, 25694125, 20979234, 11502806) and is extremely rare in the general population. Other reports have also observed different changes at the same amino acid in patients with medullary thyroid carcinoma (PMID:7874109, 7849720). This c.1858T>G (p.Cys620Gly) variant in the RET gene is classified as pathogenic.
Research and Development, ARUP Laboratories RCV000609889 SCV000042466 pathogenic Multiple endocrine neoplasia, type 2 2018-05-04 no assertion criteria provided literature only Three family reports, 13 have the mutation genotype: 7 MTC, 1 Pheo, and 4 HSCR (PMID 20979234). Youngest with MTC: 22 yr. Additional references: PMID 11073534, 11502806 and 14718397.

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.