ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1867G>A (p.Glu623Lys)

gnomAD frequency: 0.00003  dbSNP: rs377767402
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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 RCV000575097 SCV000674857 benign Hereditary cancer-predisposing syndrome 2016-11-29 criteria provided, single submitter clinical testing This alteration is classified as 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.
Mendelics RCV000988343 SCV001138026 likely benign Multiple endocrine neoplasia type 2A 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001369787 SCV001566236 uncertain significance Multiple endocrine neoplasia, type 2 2024-01-28 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 623 of the RET protein (p.Glu623Lys). This variant is present in population databases (rs377767402, gnomAD 0.02%). This missense change has been observed in individual(s) with medullary thyroid cancer (PMID: 15858153). ClinVar contains an entry for this variant (Variation ID: 24906). 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.
GeneDx RCV001762053 SCV002001090 uncertain significance not provided 2024-03-08 criteria provided, single submitter clinical testing Observed in a family with medullary thyroid carcinoma but did not segregate with disease, indicating that this variant is unlikely to be associated with increased risk for Multiple Endocrine Neoplasia type 2/Familial Medullary Thyroid Carcinoma (PMID: 15858153); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 9068588, 16849421, 14633923, 32284345, 32091409, 15858153)
Myriad Genetics, Inc. RCV000988343 SCV005403668 likely benign Multiple endocrine neoplasia type 2A 2024-08-09 criteria provided, single submitter clinical testing This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.

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