Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000553962 | SCV000631683 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2022-09-12 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 366 of the PLOD1 protein (p.Ala366Val). This variant is present in population databases (rs377080927, gnomAD 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: 459802). 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 valine 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 | RCV002456082 | SCV002736239 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-12-09 | criteria provided, single submitter | clinical testing | The p.A366V variant (also known as c.1097C>T), located in coding exon 10 of the PLOD1 gene, results from a C to T substitution at nucleotide position 1097. The alanine at codon 366 is replaced by valine, an amino acid with similar properties. However, this change occurs in the last base pair of coding exon 10 and may have some effect on normal mRNA splicing. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. This amino acid position is not well conserved in available vertebrate species, and valine is the reference amino acid in other vertebrate species. In addition, as a missense substitution this 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. |