Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000437943 | SCV000536628 | uncertain significance | not provided | 2017-01-31 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the FBN2 gene. The L900F variant has notbeen published as pathogenic or been reported as benign to our knowledge. This variant is not observedin large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome VariantServer). This substitution occurs at a position that is conserved across species, and in silico analysispredicts this variant is probably damaging to the protein structure/function. However, to ourknowledge no studies have been performed to determine the functional effect of the L900F variant.The L900F variant is a conservative amino acid substitution, which is not likely to impact secondaryprotein structure as these residues share similar properties. Furthermore, L900F does not affect aCysteine residue within a calcium-binding EGF-like domain of the FBN2 gene. Cysteine substitutions inthe calcium-binding EGF-like domains represent the majority of pathogenic missense changesassociated with congenital arachnodactyly (Collod-Beroud et al., 2003; Frédéric et al., 2009). |
Ambry Genetics | RCV002429462 | SCV002742708 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-04-28 | criteria provided, single submitter | clinical testing | The p.L900F variant (also known as c.2698C>T), located in coding exon 21 of the FBN2 gene, results from a C to T substitution at nucleotide position 2698. The leucine at codon 900 is replaced by phenylalanine, an amino acid with highly similar properties, and is located in the hybrid motif #2 domain. This amino acid position is highly 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. |