Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001755546 | SCV002005092 | uncertain significance | not provided | 2023-03-25 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25650308) |
| Fulgent Genetics, |
RCV002482287 | SCV002787387 | uncertain significance | Acute myeloid leukemia; Tatton-Brown-Rahman overgrowth syndrome; Heyn-Sproul-Jackson syndrome | 2021-08-06 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003772097 | SCV004662193 | uncertain significance | Tatton-Brown-Rahman overgrowth syndrome | 2023-03-27 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 219 of the DNMT3A protein (p.Lys219Arg). This variant is not present in population databases (gnomAD no frequency). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DNMT3A protein function. ClinVar contains an entry for this variant (Variation ID: 1318898). This missense change has been observed in individual(s) with DNMT3A-related conditions (PMID: 25650308). |