Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001298377 | SCV001487432 | uncertain significance | Pyruvate dehydrogenase E2 deficiency | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with glycine at codon 469 of the DLAT protein (p.Glu469Gly). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (rs376141049, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with DLAT-related conditions. 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 DLAT 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 | RCV003355363 | SCV004053033 | uncertain significance | Inborn genetic diseases | 2023-08-04 | criteria provided, single submitter | clinical testing | The c.1406A>G (p.E469G) alteration is located in exon 11 (coding exon 11) of the DLAT gene. This alteration results from a A to G substitution at nucleotide position 1406, causing the glutamic acid (E) at amino acid position 469 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |