ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1452G>C (p.Met484Ile)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002643131 SCV002987937 uncertain significance Multiple endocrine neoplasia, type 2 2024-05-12 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 484 of the RET protein (p.Met484Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 1941410). 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.
Ambry Genetics RCV004673700 SCV005157005 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-14 criteria provided, single submitter clinical testing The p.M484I variant (also known as c.1452G>C), located in coding exon 7 of the RET gene, results from a G to C substitution at nucleotide position 1452. The methionine at codon 484 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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