ClinVar Miner

Submissions for variant NM_000302.4(PLOD1):c.2162C>T (p.Ala721Val)

gnomAD frequency: 0.00007  dbSNP: rs149161535
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414684 SCV000492212 uncertain significance not specified 2016-11-28 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the PLOD1 gene. The A721V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed at a significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, the A721V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Alanine are tolerated across species, and Valine is the wild-type amino acid at this position in at least one species. Furthermore, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Invitae RCV000705331 SCV000834323 uncertain significance Ehlers-Danlos syndrome, kyphoscoliotic type 1 2022-07-04 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 721 of the PLOD1 protein (p.Ala721Val). This variant is present in population databases (rs149161535, 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: 373603). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV002429342 SCV002727340 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2018-12-04 criteria provided, single submitter clinical testing The p.A721V variant (also known as c.2162C>T), located in coding exon 19 of the PLOD1 gene, results from a C to T substitution at nucleotide position 2162. The alanine at codon 721 is replaced by valine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, valine 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.