ClinVar Miner

Submissions for variant NM_020975.6(RET):c.3302T>C (p.Leu1101Pro)

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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 RCV002691191 SCV002999723 uncertain significance Multiple endocrine neoplasia, type 2 2022-09-30 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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 present in population databases (rs769570496, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1101 of the RET protein (p.Leu1101Pro).
Ambry Genetics RCV003273988 SCV004009501 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-08 criteria provided, single submitter clinical testing The p.L1101P variant (also known as c.3302T>C), located in coding exon 20 of the RET gene, results from a T to C substitution at nucleotide position 3302. The leucine at codon 1101 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. 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 RCV002691191 SCV005430419 uncertain significance Multiple endocrine neoplasia, type 2 2024-02-22 criteria provided, single submitter clinical testing This missense variant replaces leucine with proline at codon 1101 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 been identified in 1/251496 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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