ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.8058C>A (p.Phe2686Leu)

gnomAD frequency: 0.00006  dbSNP: rs150734807
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000221212 SCV000279903 uncertain significance not provided 2016-02-19 criteria provided, single submitter clinical testing The F2686L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. This substitution occurs at a position that is conserved through mammals. However, the F2686L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Furthermore, although the F2686L variant resides within a calcium-binding EGF-like domain of the FBN2 gene, it does not affect a Cysteine residue. Cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with Marfan syndrome (Collod-Beroud et al., 2003; Frédéric et al., 2009). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Labcorp Genetics (formerly Invitae), Labcorp RCV000824483 SCV000965382 benign Congenital contractural arachnodactyly 2023-07-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV002417979 SCV002677537 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-08-22 criteria provided, single submitter clinical testing The p.F2686L variant (also known as c.8058C>A), located in coding exon 63 of the FBN2 gene, results from a C to A substitution at nucleotide position 8058. The phenylalanine at codon 2686 is replaced by leucine, an amino acid with highly similar properties, and is located in the cb EGF-like #43 domain. This amino acid position is 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.

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