ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2304G>C (p.Glu768Asp) (rs78014899)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001015022 SCV001175806 pathogenic Hereditary cancer-predisposing syndrome 2019-03-08 criteria provided, single submitter clinical testing Deficient protein function in appropriate functional assay(s);Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Good segregation with disease (lod 1.5-3 = 5-9 meioses)
Invitae RCV000021842 SCV001226408 likely pathogenic Multiple endocrine neoplasia, type 2 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 768 of the RET protein (p.Glu768Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with medullary thyroid carcinoma (PMID: 12116277, 9263528, 11230481, 15855933, 16736292, 17097365, 18062802). ClinVar contains an entry for this variant (Variation ID: 13931). This variant has been reported to have conflicting or insufficient data to determine the effect on RET protein function (PMID: 15184865, 26046350, 17047083, 14715928). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000014956 SCV000035212 pathogenic Familial medullary thyroid carcinoma 2002-06-01 no assertion criteria provided literature only
Research and Development, ARUP Laboratories RCV000021842 SCV000042508 pathogenic Multiple endocrine neoplasia, type 2 2018-05-04 no assertion criteria provided literature only FMTC phenotype is more common, only one report of Pheo (PMID 15855933). Youngest with MTC: 22 yr. In vitro studies: RET activation (PMID 9242375). Additional references: PMID 7784092, 18062802, 9111992 and 15531714.
Database of Curated Mutations (DoCM) RCV000431893 SCV000505642 likely pathogenic Neoplasm 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439063 SCV000505643 likely pathogenic Multiple endocrine neoplasia, type 4 2016-05-13 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421871 SCV000505644 likely pathogenic Medullary thyroid carcinoma 2016-05-13 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432579 SCV000505645 likely pathogenic Multiple endocrine neoplasia, type 2a 2016-05-13 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000445341 SCV000505646 likely pathogenic Multiple endocrine neoplasia, type 1 2016-05-13 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426010 SCV000505647 likely pathogenic Multiple endocrine neoplasia, type 2b 2016-05-13 no assertion criteria provided literature only

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