Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003067515 | SCV003457470 | uncertain significance | Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency | 2022-05-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 537 of the DNMT3B protein (p.Arg537Trp). This variant is present in population databases (rs771223602, gnomAD 0.04%). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25". The tryptophan 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 | RCV003274202 | SCV003987020 | uncertain significance | Inborn genetic diseases | 2023-05-31 | criteria provided, single submitter | clinical testing | The c.1609C>T (p.R537W) alteration is located in exon 15 (coding exon 14) of the DNMT3B gene. This alteration results from a C to T substitution at nucleotide position 1609, causing the arginine (R) at amino acid position 537 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |