ClinVar Miner

Submissions for variant NM_177438.3(DICER1):c.3709C>T (p.Leu1237Phe)

dbSNP: rs757460313
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001020936 SCV001182482 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-16 criteria provided, single submitter clinical testing The p.L1237F variant (also known as c.3709C>T), located in coding exon 20 of the DICER1 gene, results from a C to T substitution at nucleotide position 3709. The leucine at codon 1237 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001065079 SCV001230018 uncertain significance DICER1-related tumor predisposition 2024-05-19 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1237 of the DICER1 protein (p.Leu1237Phe). This variant is present in population databases (rs757460313, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with DICER1-related conditions. ClinVar contains an entry for this variant (Variation ID: 824104). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DICER1 protein function with a negative predictive value of 80%. 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.
Hereditary Cancer Group, L’Institut d'Investigació Biomèdica de Bellvitge RCV001020936 SCV005442469 uncertain significance Hereditary cancer-predisposing syndrome 2024-12-19 criteria provided, single submitter clinical testing PM2_supporting, BP4

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