Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002315158 | SCV000739547 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-12-07 | criteria provided, single submitter | clinical testing | The p.D382G variant (also known as c.1145A>G), located in coding exon 11 of the PLOD1 gene, results from an A to G substitution at nucleotide position 1145. The aspartic acid at codon 382 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV002531845 | SCV003281955 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2022-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 382 of the PLOD1 protein (p.Asp382Gly). 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 PLOD1 protein function. ClinVar contains an entry for this variant (Variation ID: 520114). This variant has not been reported in the literature in individuals affected with PLOD1-related conditions. This variant is not present in population databases (gnomAD no frequency). |