Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001228744 | SCV001401160 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 718 of the PLOD1 protein (p.Arg718Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs754650948, ExAC 0.002%). 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: "Probably Damaging"; 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 | RCV002429973 | SCV002727009 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-04-03 | criteria provided, single submitter | clinical testing | The p.R718C variant (also known as c.2152C>T), located in coding exon 19 of the PLOD1 gene, results from a C to T substitution at nucleotide position 2152. The arginine at codon 718 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |