Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000814927 | SCV000955365 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2022-07-05 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 699 of the PLOD1 protein (p.Met699Val). This variant is present in population databases (rs142916043, gnomAD 0.005%). 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: 658162). 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 | RCV002422820 | SCV002730324 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-04-19 | criteria provided, single submitter | clinical testing | The p.M699V variant (also known as c.2095A>G), located in coding exon 19 of the PLOD1 gene, results from an A to G substitution at nucleotide position 2095. The methionine at codon 699 is replaced by valine, 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. |