ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2261C>T (p.Thr754Met) (rs181856591)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000573705 SCV000674805 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Counsyl RCV000410377 SCV000489733 uncertain significance Multiple endocrine neoplasia, type 2b 2015-11-21 criteria provided, single submitter clinical testing
Counsyl RCV000411486 SCV000489734 uncertain significance Multiple endocrine neoplasia, type 2a 2015-11-21 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000202914 SCV000258170 uncertain significance Multiple endocrine neoplasia 2015-02-13 criteria provided, single submitter clinical testing
ITMI RCV000121979 SCV000086189 not provided not specified 2013-09-19 no assertion provided reference population
Invitae RCV000462996 SCV000543817 uncertain significance Multiple endocrine neoplasia, type 2 2018-11-21 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 754 of the RET protein (p.Thr754Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs181856591, ExAC 0.01%). This variant has not been reported in the literature in individuals with RET-related disease. ClinVar contains an entry for this variant (Variation ID: 135177). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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