Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000805932 | SCV000945907 | uncertain significance | Tatton-Brown-Rahman overgrowth syndrome | 2023-07-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 688 of the DNMT3A protein (p.Arg688His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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 expected to disrupt DNMT3A protein function. ClinVar contains an entry for this variant (Variation ID: 650730). This missense change has been observed in individual(s) with clinical features of Tatton-Brown-Rahman syndrome (PMID: 34092059, 34315901). |
| Ambry Genetics | RCV001267190 | SCV001445371 | uncertain significance | Inborn genetic diseases | 2017-11-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001567102 | SCV001790733 | pathogenic | not provided | 2020-06-08 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |