ClinVar Miner

Submissions for variant NM_001130823.3(DNMT1):c.857T>C (p.Val286Ala)

gnomAD frequency: 0.00003  dbSNP: rs766504703
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000694576 SCV000823027 uncertain significance Hereditary sensory neuropathy-deafness-dementia syndrome 2022-01-23 criteria provided, single submitter clinical testing 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. This variant has not been reported in the literature in individuals affected with DNMT1-related conditions. This variant is present in population databases (rs766504703, gnomAD 0.004%). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 286 of the DNMT1 protein (p.Val286Ala). ClinVar contains an entry for this variant (Variation ID: 573027). 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 alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function.
Mayo Clinic Laboratories, Mayo Clinic RCV001507409 SCV001712949 uncertain significance not provided 2019-10-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV002422518 SCV002677112 uncertain significance Inborn genetic diseases 2022-01-05 criteria provided, single submitter clinical testing The p.V270A variant (also known as c.809T>C), located in coding exon 10 of the DNMT1 gene, results from a T to C substitution at nucleotide position 809. The valine at codon 270 is replaced by alanine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002485677 SCV002778297 uncertain significance Autosomal dominant cerebellar ataxia, deafness and narcolepsy; Hereditary sensory neuropathy-deafness-dementia syndrome 2021-07-21 criteria provided, single submitter clinical testing

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.