ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1901G>T (p.Cys634Phe) (rs75996173)

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
Invitae RCV000471652 SCV000543841 pathogenic Multiple endocrine neoplasia, type 2 2020-03-12 criteria provided, single submitter clinical testing This sequence change replaces cysteine with phenylalanine at codon 634 of the RET protein (p.Cys634Phe). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and phenylalanine. This variant is present in population databases (rs75996173, ExAC 0.01%). This variant has been reported in the literature co-segregating with disease in several families (PMID: 8099202, 24716929, 24684035, 20739875, 17895320, 25628771) as well as present in multiple unrelated individuals affected with multiple endocrine neoplasia type 2A (MEN2A), medullary thyroid cancer (MTC) (PMID: 16865647, 18062802, 25440022) and pheochromocytoma (PMID: 12000816). ClinVar contains an entry for this variant (Variation ID: 13911). This variant affects a highly conserved and functionally important cysteine amino acid residue of the RET protein. This residue is one of the most commonly altered codons in individuals affected with MEN2A (PMID: 8099202, 12000816, 21765987, 25440022). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000014928 SCV000035184 pathogenic Multiple endocrine neoplasia, type 2a 2002-05-09 no assertion criteria provided literature only
OMIM RCV000014929 SCV000035185 pathogenic Familial medullary thyroid carcinoma 2002-05-09 no assertion criteria provided literature only
OMIM RCV000014930 SCV000035186 pathogenic Pheochromocytoma 2002-05-09 no assertion criteria provided literature only
Research and Development, ARUP Laboratories RCV000471652 SCV000042491 pathogenic Multiple endocrine neoplasia, type 2 2018-05-04 no assertion criteria provided literature only MEN2A or FMTC families. Youngest with MTC: 7 yr. Youngest with Pheo: 26 yr (PMID 25629635). Patients may also have cutaneous lichen amyloidosis (PMID 7874109). In the oldest reference, codon 634 was called codon 380. Additional references: PMID 16712668, 11900218, 15452453, 12604374 and 11524247.

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.