ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1046C>A (p.Ala349Glu)

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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 RCV004947376 SCV005492779 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-20 criteria provided, single submitter clinical testing The p.A349E variant (also known as c.1046C>A), located in coding exon 5 of the RET gene, results from a C to A substitution at nucleotide position 1046. The alanine at codon 349 is replaced by glutamic acid, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV005107805 SCV005774303 uncertain significance Multiple endocrine neoplasia, type 2 2025-01-23 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 349 of the RET protein (p.Ala349Glu). 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. 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.

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