ClinVar Miner

Submissions for variant NM_177438.3(DICER1):c.832C>T (p.Leu278Phe)

dbSNP: rs768248216
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Pleuropulmonary Blastoma Registry, Children's Hospitals and Clinics of Minnesota RCV000240941 SCV000195641 pathogenic DICER1-related tumor predisposition 2014-11-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV002436077 SCV002677145 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-08 criteria provided, single submitter clinical testing The p.L278F variant (also known as c.832C>T), located in coding exon 6 of the DICER1 gene, results from a C to T substitution at nucleotide position 832. The leucine at codon 278 is replaced by phenylalanine, an amino acid with highly similar properties. This variant has been reported as a germline mosaic finding in 1/124 children with pleuropulmonary blastoma (Brenneman M et al. F1000Res, 2015 Jul;4:214). This amino acid position is highly 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 alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000240941 SCV004614554 uncertain significance DICER1-related tumor predisposition 2023-02-01 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. 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. ClinVar contains an entry for this variant (Variation ID: 254354). This missense change has been observed in individual(s) with pleuropulmonary blastoma (PMID: 26925222). This variant is present in population databases (rs768248216, gnomAD 0.003%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 278 of the DICER1 protein (p.Leu278Phe).

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