ClinVar Miner

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

gnomAD frequency: 0.00003  dbSNP: rs377767420
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Total submissions: 9
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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 likely benign Hereditary cancer-predisposing syndrome 2022-09-02 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV000799360 SCV000939019 uncertain significance Multiple endocrine neoplasia, type 2 2024-01-14 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 818 of the RET protein (p.Glu818Lys). This variant is present in population databases (rs377767420, gnomAD 0.01%). This missense change has been observed in individual(s) with medullary thyroid carcinoma (PMID: 18058472). ClinVar contains an entry for this variant (Variation ID: 24943). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Sema4, Sema4 RCV000571277 SCV002529978 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-17 criteria provided, single submitter curation
Fulgent Genetics, Fulgent Genetics RCV002490401 SCV002788824 uncertain significance Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A 2021-08-25 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000411157 SCV004018475 uncertain significance Multiple endocrine neoplasia type 2A 2023-04-18 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics RCV003460490 SCV004208696 uncertain significance Hirschsprung disease, susceptibility to, 1 2024-03-09 criteria provided, single submitter clinical testing
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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