ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1258G>T (p.Ala420Ser)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV003376975 SCV004095548 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-06 criteria provided, single submitter clinical testing The p.A420S variant (also known as c.1258G>T), located in coding exon 6 of the RET gene, results from a G to T substitution at nucleotide position 1258. The alanine at codon 420 is replaced by serine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV005061343 SCV005720899 uncertain significance Multiple endocrine neoplasia, type 2 2024-09-19 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 420 of the RET protein (p.Ala420Ser). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 2618978). 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 disruptive. 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.

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