ClinVar Miner

Submissions for variant NM_020975.6(RET):c.3271C>A (p.Pro1091Thr)

dbSNP: rs1564502605
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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 RCV000693763 SCV000821644 uncertain significance Multiple endocrine neoplasia, type 2 2024-11-18 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1091 of the RET protein (p.Pro1091Thr). 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: 572394). 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.
All of Us Research Program, National Institutes of Health RCV000693763 SCV004830402 uncertain significance Multiple endocrine neoplasia, type 2 2023-09-04 criteria provided, single submitter clinical testing This missense variant replaces proline with threonine at codon 1091 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.
Ambry Genetics RCV004669081 SCV005156991 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-12 criteria provided, single submitter clinical testing The p.P1091T variant (also known as c.3271C>A), located in coding exon 20 of the RET gene, results from a C to A substitution at nucleotide position 3271. The proline at codon 1091 is replaced by threonine, an amino acid with highly 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.

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