ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1441C>G (p.Leu481Val)

gnomAD frequency: 0.00005  dbSNP: rs767210575
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000524715 SCV000658405 uncertain significance Multiple endocrine neoplasia, type 2 2024-01-21 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 481 of the RET protein (p.Leu481Val). This variant is present in population databases (rs767210575, gnomAD 0.07%). This missense change has been observed in individual(s) with medullary thyroid carcinoma (PMID: 33827484). ClinVar contains an entry for this variant (Variation ID: 477316). 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.
Counsyl RCV000662529 SCV000785094 uncertain significance Multiple endocrine neoplasia type 2A 2018-05-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV001011599 SCV001171938 likely benign Hereditary cancer-predisposing syndrome 2023-10-03 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.
All of Us Research Program, National Institutes of Health RCV000524715 SCV004823454 likely benign Multiple endocrine neoplasia, type 2 2024-01-04 criteria provided, single submitter clinical testing

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