Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000520100 | SCV000619325 | uncertain significance | not provided | 2017-07-18 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the FBN2 gene. The P733R variant has not been published as pathogenic or been reported as benign to our knowledge. However, it has been observed in 6/11512 (0.05%) alleles from individuals of Latino ancestry in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P733R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved in mammals and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, P733R does not affect a Cysteine residue within a calcium-binding EGF-like domain of the FBN2 gene. Cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN2-relatied disorders (Frederic et al., 2009). |
Invitae | RCV001240363 | SCV001413299 | likely benign | Congenital contractural arachnodactyly | 2022-07-05 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002420314 | SCV002724956 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-06-06 | criteria provided, single submitter | clinical testing | The p.P733R variant (also known as c.2198C>G), located in coding exon 16 of the FBN2 gene, results from a C to G substitution at nucleotide position 2198. The proline at codon 733 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |