Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000814036 | SCV000954428 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2021-10-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 136 of the PLOD1 protein (p.Arg136His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). 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: "Possibly 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 | RCV003279095 | SCV004003440 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-04-24 | criteria provided, single submitter | clinical testing | The p.R136H variant (also known as c.407G>A), located in coding exon 4 of the PLOD1 gene, results from a G to A substitution at nucleotide position 407. The arginine at codon 136 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |