ClinVar Miner

Submissions for variant NM_177438.3(DICER1):c.4795C>G (p.Arg1599Gly)

gnomAD frequency: 0.00003  dbSNP: rs587778230
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000532384 SCV000658305 uncertain significance DICER1-related tumor predisposition 2025-01-14 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1599 of the DICER1 protein (p.Arg1599Gly). This variant is present in population databases (rs587778230, gnomAD 0.003%). This missense change has been observed in individual(s) with ependymoma (PMID: 26580448). ClinVar contains an entry for this variant (Variation ID: 477218). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt DICER1 protein function with a negative predictive value of 95%. 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 RCV000562129 SCV000661918 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-16 criteria provided, single submitter clinical testing The p.R1599G variant (also known as c.4795C>G), located in coding exon 22 of the DICER1 gene, results from a C to G substitution at nucleotide position 4795. The arginine at codon 1599 is replaced by glycine, an amino acid with dissimilar properties. This variant has been reported in 1/1120 pediatric cancer patient who underwent whole genome sequencing and/or whole exome sequencing; this patient was diagnosed with ependymoma (Zhang J et al. N Engl J Med, 2015 Dec;373:2336-2346). This amino acid position is not well conserved in available vertebrate species. 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.

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