ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1907C>T (p.Thr636Met) (rs1035958105)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000463920 SCV000543837 uncertain significance Multiple endocrine neoplasia, type 2 2018-08-06 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 636 of the RET protein (p.Thr636Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with medullary thyroid carcinoma (PMID: 25725622). ClinVar contains an entry for this variant (Variation ID: 405553). Experimental studies have shown that this missense change stimulates cell proliferation and leads to a loss of contact inhibition and increased cell migration, although these effects on protein function were milder than those seen with the positive control (PMID: 25725622). 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 RCV000570272 SCV000674859 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Mendelics RCV000709117 SCV000838391 uncertain significance Multiple endocrine neoplasia, type 2a 2018-07-02 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV000664363 SCV000788289 uncertain significance not specified 2018-05-04 no assertion criteria provided literature only Single individual report: MTC only (78 yr)

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