ClinVar Miner

Submissions for variant NM_001130823.3(DNMT1):c.406C>T (p.Arg136Cys) (rs138841970)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000221683 SCV000279276 likely benign not specified 2017-04-11 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.
Illumina Clinical Services Laboratory,Illumina RCV000549690 SCV000410264 benign Hereditary sensory neuropathy type IE 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV000549690 SCV000651308 uncertain significance Hereditary sensory neuropathy type IE 2020-07-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 136 of the DNMT1 protein (p.Arg136Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs138841970, ExAC 0.04%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in an individual affected with Beckwith-Wiedemann syndrome that was inherited from an unaffected parent (PMID: 30165906). ClinVar contains an entry for this variant (Variation ID: 234461). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000996738 SCV001151625 uncertain significance not provided 2018-06-01 criteria provided, single submitter clinical testing
Genetics and Molecular Pathology Laboratory,Hudson Institute of Medical Research RCV000625705 SCV000599434 uncertain significance Beckwith-Wiedemann syndrome no assertion criteria provided research This variant was identified in heterozygous form in 1 of 51 cases with Beckwith Wiedemann syndrome with loss of methylation at KCNQ1OT1 at Imprinting centre 2 on 11p15.5. The variant was maternally inherited. The variant frequency in dbSNP147 is 0.00028.

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.