ClinVar Miner

Submissions for variant NM_020975.6(RET):c.3332C>T (p.Thr1111Met)

gnomAD frequency: 0.00001  dbSNP: rs1003057639
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001238151 SCV001410950 uncertain significance Multiple endocrine neoplasia, type 2 2023-06-07 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 964019). 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. 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. 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 methionine, which is neutral and non-polar, at codon 1111 of the RET protein (p.Thr1111Met).
Mendelics RCV002246228 SCV002519931 benign not specified 2022-05-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV002322139 SCV002605578 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-28 criteria provided, single submitter clinical testing The p.T1111M variant (also known as c.3332C>T), located in coding exon 20 of the RET gene, results from a C to T substitution at nucleotide position 3332. The threonine at codon 1111 is replaced by methionine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. 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.
Baylor Genetics RCV003462806 SCV004208708 uncertain significance Hirschsprung disease, susceptibility to, 1 2023-08-15 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001238151 SCV004838739 uncertain significance Multiple endocrine neoplasia, type 2 2024-01-11 criteria provided, single submitter clinical testing This missense variant replaces threonine with methionine at codon 1111 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 hereditary cancer 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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