Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Diagnostic Laboratory, |
RCV001260609 | SCV001437701 | uncertain significance | Intellectual disability | 2020-09-10 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001879994 | SCV002183498 | uncertain significance | Tatton-Brown-Rahman overgrowth syndrome | 2021-09-04 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 981258). This variant has not been reported in the literature in individuals affected with DNMT3A-related conditions. This variant is present in population databases (rs760854242, ExAC 0.007%). This sequence change replaces glycine with arginine at codon 332 of the DNMT3A protein (p.Gly332Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. |
Institute of Human Genetics Munich, |
RCV001879994 | SCV002764673 | likely pathogenic | Tatton-Brown-Rahman overgrowth syndrome | 2021-03-10 | criteria provided, single submitter | clinical testing |