Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000535292 | SCV000631736 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2022-03-11 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 269 of the PLOD1 protein (p.Val269Met). This variant is present in population databases (rs145447578, gnomAD 0.007%). 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: 459829). 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 | RCV002314968 | SCV000739537 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-11-17 | criteria provided, single submitter | clinical testing | The p.V269M variant (also known as c.805G>A), located in coding exon 8 of the PLOD1 gene, results from a G to A substitution at nucleotide position 805. The valine at codon 269 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, methionine is the reference amino acid in other vertebrate species. 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. |
| ARUP Laboratories, |
RCV000535292 | SCV001472402 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2020-02-07 | criteria provided, single submitter | clinical testing | The PLOD1 c.805G>A; p.Val269Met variant (rs145447578), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 459829). This variant is found on only eight chromosomes (8/251438 alleles) in the Genome Aggregation Database. The valine at codon 269 is highly conserved but computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, due to limited information, the clinical significance of the p.Val269Met variant is uncertain at this time. |
| Gene |
RCV001574577 | SCV001801426 | uncertain significance | not provided | 2020-01-14 | criteria provided, single submitter | clinical testing | Has not been previously reported as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 459829; Landrum et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28492532) |
| Fulgent Genetics, |
RCV000535292 | SCV002797018 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2021-11-08 | criteria provided, single submitter | clinical testing |