ClinVar Miner

Submissions for variant NM_006892.4(DNMT3B):c.568C>T (p.Arg190Cys)

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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 RCV002967313 SCV003284691 uncertain significance Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency 2024-12-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 190 of the DNMT3B protein (p.Arg190Cys). This variant is present in population databases (rs140395707, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DNMT3B-related conditions. ClinVar contains an entry for this variant (Variation ID: 2072715). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DNMT3B protein function. 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 RCV002967314 SCV003633647 uncertain significance Inborn genetic diseases 2021-03-18 criteria provided, single submitter clinical testing The c.568C>T (p.R190C) alteration is located in exon 6 (coding exon 5) of the DNMT3B gene. This alteration results from a C to T substitution at nucleotide position 568, causing the arginine (R) at amino acid position 190 to be replaced by a cysteine (C). The p.R190C alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003418683 SCV004117367 uncertain significance DNMT3B-related disorder 2023-08-15 criteria provided, single submitter clinical testing The DNMT3B c.568C>T variant is predicted to result in the amino acid substitution p.Arg190Cys. This variant was reported in an individual with Hirschsprung disease (Torroglosa et al 2014. PubMed ID: 24577265). This variant is reported in 0.020% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/20-31375171-C-T). 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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