Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000703539 | SCV000832442 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2022-07-05 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 406 of the PLOD1 protein (p.Pro406Ser). This variant is present in population databases (rs760764359, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with PLOD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 580095). 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. 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 | RCV002352200 | SCV002661095 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-12-16 | criteria provided, single submitter | clinical testing | The p.P406S variant (also known as c.1216C>T), located in coding exon 12 of the PLOD1 gene, results from a C to T substitution at nucleotide position 1216. The proline at codon 406 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. 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. |