ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2641C>G (p.Leu881Val) (rs377767427)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569942 SCV000664472 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Rarity in general population databases (dbsnp, esp, 1000 genomes),Other data supporting pathogenic classification
Counsyl RCV000410267 SCV000489787 uncertain significance Multiple endocrine neoplasia, type 2b 2016-02-16 criteria provided, single submitter clinical testing
Counsyl RCV000410921 SCV000489788 uncertain significance Multiple endocrine neoplasia, type 2a 2016-02-16 criteria provided, single submitter clinical testing
Invitae RCV000466832 SCV000543803 uncertain significance Multiple endocrine neoplasia, type 2 2018-12-14 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 881 of the RET protein (p.Leu881Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs377767427, ExAC 0.006%). This variant has been reported in an individual with medullary thyroid carcinoma and her son with C-cell hyperplasia, as well as other family members who were not affected with cancer (PMID: 20013610). ClinVar contains an entry for this variant (Variation ID: 24957). 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.
Research and Development, ARUP Laboratories RCV000021871 SCV000042537 uncertain significance not specified 2018-05-04 no assertion criteria provided literature only Single family report, 6 have the variant genotype: 1 metastatic MTC (46yr), 1 uni-lateral/uni-focal C-cell hyperplasia (20 yr), 1 had normal thyroid (17yr), 1 elevated calcitonin (43yr), and 2 asymptomatic upon screening (>70 yr). Additional references: MEN2008 meeting poster 26 http://www.hormones.gr/preview.php?c_id=628.

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