ClinVar Miner

Submissions for variant NM_177438.3(DICER1):c.3329T>G (p.Ile1110Ser)

gnomAD frequency: 0.00001  dbSNP: rs759760077
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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 RCV000458245 SCV000553506 uncertain significance DICER1-related tumor predisposition 2025-01-17 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1110 of the DICER1 protein (p.Ile1110Ser). This variant is present in population databases (rs759760077, gnomAD 0.005%). 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: 412051). 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%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (internal data). 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 RCV000561530 SCV000669328 likely benign Hereditary cancer-predisposing syndrome 2024-05-31 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Sema4, Sema4 RCV000561530 SCV002532542 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-11 criteria provided, single submitter curation

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