Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001214584 | SCV001386270 | uncertain significance | Hereditary sensory neuropathy-deafness-dementia syndrome | 2022-10-01 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 944228). This variant has not been reported in the literature in individuals affected with DNMT1-related conditions. This variant is present in population databases (rs146516082, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 119 of the DNMT1 protein (p.Arg119Gly). |
Genetic Services Laboratory, |
RCV001815026 | SCV002061956 | uncertain significance | not specified | 2017-10-03 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002339561 | SCV002618893 | uncertain significance | Inborn genetic diseases | 2020-07-21 | criteria provided, single submitter | clinical testing | The p.R119G variant (also known as c.355A>G), located in coding exon 4 of the DNMT1 gene, results from an A to G substitution at nucleotide position 355. The arginine at codon 119 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is not well 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. |