ClinVar Miner

Submissions for variant NM_177438.3(DICER1):c.3635A>C (p.Gln1212Pro)

dbSNP: rs763415569
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000539806 SCV000658237 uncertain significance DICER1-related tumor predisposition 2024-04-09 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1212 of the DICER1 protein (p.Gln1212Pro). This variant is present in population databases (rs763415569, gnomAD 0.0009%). 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: 477151). 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.
Ambry Genetics RCV002456262 SCV002617750 uncertain significance Hereditary cancer-predisposing syndrome 2022-07-21 criteria provided, single submitter clinical testing The p.Q1212P variant (also known as c.3635A>C), located in coding exon 20 of the DICER1 gene, results from an A to C substitution at nucleotide position 3635. The glutamine at codon 1212 is replaced by proline, an amino acid with 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.
Fulgent Genetics, Fulgent Genetics RCV005010532 SCV005637562 uncertain significance Euthyroid goiter; Rhabdomyosarcoma, embryonal, 2; Pleuropulmonary blastoma; Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome 2024-04-25 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004742503 SCV005360558 uncertain significance DICER1-related disorder 2024-03-29 no assertion criteria provided clinical testing The DICER1 c.3635A>C variant is predicted to result in the amino acid substitution p.Gln1212Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/477151/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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