Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001223758 | SCV001395920 | uncertain significance | Hereditary sensory neuropathy-deafness-dementia syndrome | 2022-08-16 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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"). ClinVar contains an entry for this variant (Variation ID: 951773). This missense change has been observed in individual(s) with clinical features of DNMT1-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1011 of the DNMT1 protein (p.Arg1011Gln). |
Ambry Genetics | RCV002436870 | SCV002751412 | uncertain significance | Inborn genetic diseases | 2021-02-17 | criteria provided, single submitter | clinical testing | The p.R995Q variant (also known as c.2984G>A), located in coding exon 28 of the DNMT1 gene, results from a G to A substitution at nucleotide position 2984. The arginine at codon 995 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly 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. |