ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1613C>G (p.Thr538Arg)

gnomAD frequency: 0.00001  dbSNP: rs148406803
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001955201 SCV002207865 uncertain significance Multiple endocrine neoplasia, type 2 2024-10-02 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 538 of the RET protein (p.Thr538Arg). 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: 1434991). 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 RCV002388888 SCV002703163 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-08 criteria provided, single submitter clinical testing The p.T538R variant (also known as c.1613C>G), located in coding exon 8 of the RET gene, results from a C to G substitution at nucleotide position 1613. The threonine at codon 538 is replaced by arginine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV001955201 SCV005430342 uncertain significance Multiple endocrine neoplasia, type 2 2024-06-09 criteria provided, single submitter clinical testing This missense variant replaces threonine with arginine at codon 538 of the RET protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RET-related disorders in the literature. 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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