ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1366A>G (p.Thr456Ala)

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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 RCV002890347 SCV003242126 uncertain significance Multiple endocrine neoplasia, type 2 2022-07-30 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 456 of the RET protein (p.Thr456Ala).
Ambry Genetics RCV004946090 SCV005492793 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-12 criteria provided, single submitter clinical testing The p.T456A variant (also known as c.1366A>G), located in coding exon 7 of the RET gene, results from an A to G substitution at nucleotide position 1366. The threonine at codon 456 is replaced by alanine, an amino acid with 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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