Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001929104 | SCV002199151 | uncertain significance | Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency | 2021-08-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glutamine at codon 127 of the DNMT3B protein (p.Arg127Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs754832933, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with DNMT3B-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV003264278 | SCV003947062 | uncertain significance | Inborn genetic diseases | 2023-03-17 | criteria provided, single submitter | clinical testing | The c.380G>A (p.R127Q) alteration is located in exon 5 (coding exon 4) of the DNMT3B gene. This alteration results from a G to A substitution at nucleotide position 380, causing the arginine (R) at amino acid position 127 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |