ClinVar Miner

Submissions for variant NM_001130823.3(DNMT1):c.977A>C (p.Gln326Pro) (rs143287044)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000394305 SCV000410253 likely benign Dementia, Deafness, and Sensory Neuropathy 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000557162 SCV000651329 uncertain significance Hereditary sensory neuropathy type IE 2018-10-29 criteria provided, single submitter clinical testing This sequence change replaces glutamine with proline at codon 326 of the DNMT1 protein (p.Gln326Pro). The glutamine residue is weakly conserved and there is a moderate physicochemical difference between glutamine and proline. This variant is present in population databases (rs143287044, ExAC 0.05%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with a DNMT1-related disease. ClinVar contains an entry for this variant (Variation ID: 327919). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on DNMT1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000602957 SCV000714588 likely benign not specified 2017-10-12 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.