ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2711_2712delinsTG (p.Ser904Leu)

dbSNP: rs2538579556
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
All of Us Research Program, National Institutes of Health RCV004013450 SCV004833920 uncertain significance Multiple endocrine neoplasia, type 2 2023-07-10 criteria provided, single submitter clinical testing This missense variant replaces a serine with leucine at codon 904 of the RET protein, in a putative regulatory region of the kinase domain (PMID: 32510566). This variant has not been reported in individuals affected with RET-related disorders in the literature. A different substitution of p.Ser904Phe which resembles a phosphomimetic substitution of a phosphorylated serine has been reported to be disease-causing in ClinVar (variation ID: 24963) and reported to cause increased kinase activity and autophosphorylation in the RET protein and also an intermediate increase in the promotion of ectopic growth in a cellular assay (PMID: 21810974, 29434222). To our knowledge, functional studies have not been reported for this variant to test whether this variant substitution, p.Ser904Leu, has the same impact. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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