Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000332650 | SCV000410226 | uncertain significance | Dementia, Deafness, and Sensory Neuropathy | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001042762 | SCV001206464 | uncertain significance | Hereditary sensory neuropathy-deafness-dementia syndrome | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glutamine at codon 936 of the DNMT1 protein (p.Arg936Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs763321599, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with DNMT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 327898). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 | RCV002436180 | SCV002749040 | uncertain significance | Inborn genetic diseases | 2022-07-07 | criteria provided, single submitter | clinical testing | The p.R920Q variant (also known as c.2759G>A), located in coding exon 27 of the DNMT1 gene, results from a G to A substitution at nucleotide position 2759. The arginine at codon 920 is replaced by glutamine, an amino acid with highly similar 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. |