ClinVar Miner

Submissions for variant NM_020975.6(RET):c.770C>T (p.Pro257Leu)

dbSNP: rs1277252937
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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 RCV001051365 SCV001215515 uncertain significance Multiple endocrine neoplasia, type 2 2023-01-06 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 847756). 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 proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 257 of the RET protein (p.Pro257Leu). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV002400292 SCV002674444 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-16 criteria provided, single submitter clinical testing The p.P257L variant (also known as c.770C>T), located in coding exon 4 of the RET gene, results from a C to T substitution at nucleotide position 770. The proline at codon 257 is replaced by leucine, 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.
GeneDx RCV004721725 SCV005328094 uncertain significance not provided 2024-03-06 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 14633923)

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