ClinVar Miner

Submissions for variant NM_020975.6(RET):c.59_61dup (p.Pro20_Leu21insPro)

dbSNP: rs1064796534
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479274 SCV000573336 uncertain significance not provided 2017-02-14 criteria provided, single submitter clinical testing The c.59_61dupCGC variant has not, to our knowledge, been published in the literature as pathogenic or benign. This in-frame duplication of three nucleotides in occurs in a region that is not conserved and is not located in a known functional domain. Since in-frame duplications may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider c.59_61dupCGC to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000541134 SCV000658489 uncertain significance Multiple endocrine neoplasia, type 2 2025-01-30 criteria provided, single submitter clinical testing This variant, c.59_61dup, results in the insertion of 1 amino acid(s) of the RET protein (p.Pro20dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.06%). 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: 423618). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 RCV002356788 SCV002653657 uncertain significance Hereditary cancer-predisposing syndrome 2024-08-22 criteria provided, single submitter clinical testing The c.59_61dupCGC variant (also known as p.P20dup), located in coding exon 1 of the RET gene, results from an in-frame duplication of CGC at nucleotide positions 59 to 61. This results in the duplication of an extra proline residue between codons 20 and 21. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the available evidence, the clinical significance of this variant remains unclear.
All of Us Research Program, National Institutes of Health RCV000541134 SCV004834586 uncertain significance Multiple endocrine neoplasia, type 2 2024-03-05 criteria provided, single submitter clinical testing This variant causes an in-frame insertion of one amino acid in the RET protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 32091409). This variant has been identified in 6/142268 chromosomes 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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