Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002315157 | SCV000739545 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-11-10 | criteria provided, single submitter | clinical testing | The c.2068_2069delCGinsGT variant (also known as p.R690V), located in coding exon 19 of the PLOD1 gene, results from an in-frame deletion of CG and insertion of GT at nucleotide positions 2068 to 2069. This results in the substitution of the arginine residue for a valine residue at codon 690, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: ExAC, 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 not well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV002531844 | SCV003316884 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2022-02-18 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with valine, which is neutral and non-polar, at codon 690 of the PLOD1 protein (p.Arg690Val). 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 520113). This variant has not been reported in the literature in individuals affected with PLOD1-related conditions. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. |