ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2452G>A (p.Glu818Lys) (rs377767420)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410539 SCV000489753 uncertain significance Multiple endocrine neoplasia, type 2b 2015-12-08 criteria provided, single submitter clinical testing
Counsyl RCV000411157 SCV000489754 uncertain significance Multiple endocrine neoplasia, type 2a 2015-12-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000571277 SCV000674842 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-14 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000799360 SCV000939019 uncertain significance Multiple endocrine neoplasia, type 2 2019-12-02 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 818 of the RET protein (p.Glu818Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs377767420, ExAC 0.02%). This variant has been observed in an individual affected with medullary thyroid carcinoma (PMID: 18058472). ClinVar contains an entry for this variant (Variation ID: 24943). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000021857 SCV000042523 uncertain significance not specified 2018-05-04 no assertion criteria provided literature only Single individual report: MTC only. Listed as a codon 819 mutation in the reference.
CSER _CC_NCGL, University of Washington RCV000148782 SCV000190520 uncertain significance Medullary thyroid carcinoma 2014-06-01 no assertion criteria provided research

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