ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2530C>T (p.Arg844Trp) (rs377767424)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000662786 SCV000785595 uncertain significance Multiple endocrine neoplasia, type 2a 2017-09-29 criteria provided, single submitter clinical testing
Invitae RCV000456854 SCV000543825 uncertain significance Multiple endocrine neoplasia, type 2 2017-10-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 844 of the RET protein (p.Arg844Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Hirschsprung’s disease (PMID: 16818057). ClinVar contains an entry for this variant (Variation ID: 24950). General algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). An algorithm developed specifically for the RET gene suggest that this missense change is likely to be deleterious (PMID: 21479187). However, these predictions have not been confirmed by published functional studies. 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.
Research and Development, ARUP Laboratories RCV000021864 SCV000042530 uncertain significance not specified 2018-05-04 no assertion criteria provided literature only Germline variant found in a Korean sporadic HSCR patient. Not screened for MEN2.

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