Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000757673 | SCV000885984 | uncertain significance | not provided | 2017-06-01 | criteria provided, single submitter | clinical testing | The p.Pro258Leu variant (rs766692124) has not been reported in the medical literature and is not listed in gene-specific variant databases. It is listed in the Genome Aggregation Database (gnomAD) browser with an overall frequency of 0.002% (identified in 5 out of 277,172 chromosomes). The proline at codon 258 is highly conserved considering 12 species up to Tetraodon (Alamut software v2.9), and computational analyses suggest this variant has a significant effect on PLOD1 protein structure/function (SIFT: damaging, PolyPhen2: probably damaging, and Mutation Taster: disease causing). However, based on the available information, the clinical significance of the p.Pro258Leu variant cannot be determined with certainty. |
| Invitae | RCV001855897 | SCV002266228 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 258 of the PLOD1 protein (p.Pro258Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs766692124, ExAC 0.02%). 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: 618834). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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 | RCV002397525 | SCV002669349 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-04-09 | criteria provided, single submitter | clinical testing | The p.P258L variant (also known as c.773C>T), located in coding exon 8 of the PLOD1 gene, results from a C to T substitution at nucleotide position 773. The proline at codon 258 is replaced by leucine, an amino acid with similar 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. |