Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000707543 | SCV000836644 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2022-07-12 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 287 of the PLOD1 protein (p.Thr287Met). This variant is present in population databases (rs777957649, gnomAD 0.006%). 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: 583256). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV002442542 | SCV002681414 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-03-09 | criteria provided, single submitter | clinical testing | The p.T287M variant (also known as c.860C>T), located in coding exon 9 of the PLOD1 gene, results from a C to T substitution at nucleotide position 860. The threonine at codon 287 is replaced by methionine, an amino acid with 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. |