ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2531G>T (p.Arg844Leu) (rs55947360)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409297 SCV000490007 uncertain significance Multiple endocrine neoplasia, type 2b 2016-09-20 criteria provided, single submitter clinical testing
Counsyl RCV000410406 SCV000490008 uncertain significance Multiple endocrine neoplasia, type 2a 2016-09-20 criteria provided, single submitter clinical testing
Invitae RCV000460812 SCV000543811 uncertain significance Multiple endocrine neoplasia, type 2 2019-08-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 844 of the RET protein (p.Arg844Leu). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is present in population databases (rs55947360, ExAC 0.002%). This variant has been observed on the same chromosome with a pathogenic p.Val804Met variant in individuals affected with medullary thyroid cancer (PMID: 10826520, 28946813), and co-segregating with disease in one of the families (PMID: 10826520). ClinVar contains an entry for this variant (Variation ID: 24952). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly 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.
Research and Development, ARUP Laboratories RCV000021866 SCV000055400 uncertain significance not specified 2018-05-04 no assertion criteria provided literature only R844L was found in the germline of 57yr old melanoma patient: No mention of MEN2 screening. Has been found with another RET change, see c.[2410G>A;2531G>T].

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