Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000823685 | SCV000964553 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2022-07-27 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 560 of the PLOD1 protein (p.Ile560Val). This variant is present in population databases (rs369696269, gnomAD 0.007%). 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: 665409). 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 tolerated. 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 | RCV002397738 | SCV002710973 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-03-13 | criteria provided, single submitter | clinical testing | The p.I560V variant (also known as c.1678A>G), located in coding exon 16 of the PLOD1 gene, results from an A to G substitution at nucleotide position 1678. The isoleucine at codon 560 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, valine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |