Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000693214 | SCV000821074 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 190 of the PLOD1 protein (p.Pro190Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs375416784, ExAC 0.1%). This variant has not been reported in the literature in individuals affected with PLOD1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 | RCV002343471 | SCV002647486 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-07-31 | criteria provided, single submitter | clinical testing | The p.P190L variant (also known as c.569C>T), located in coding exon 5 of the PLOD1 gene, results from a C to T substitution at nucleotide position 569. The proline at codon 190 is replaced by leucine, an amino acid with similar properties. This amino acid position is well conserved in available 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. |