Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002315145 | SCV000739522 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-01-27 | criteria provided, single submitter | clinical testing | The p.R684C variant (also known as c.2050C>T), located in coding exon 19 of the PLOD1 gene, results from a C to T substitution at nucleotide position 2050. The arginine at codon 684 is replaced by cysteine, an amino acid with highly dissimilar properties. Based on data from ExAC, the T allele was reported in 2 of 117468 (0.002%) total alleles (Exome Aggregation Consortium (ExAC), Cambridge, MA (URL: http://exac.broadinstitute.org) [Accessed January 27, 2016). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
| Invitae | RCV001860405 | SCV002190552 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2021-06-12 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 684 of the PLOD1 protein (p.Arg684Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. 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. 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PLOD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 520101). This variant is present in population databases (rs748841458, ExAC 0.01%). |