ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.1526G>T (p.Arg509Leu) (rs199587570)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196921 SCV000250156 uncertain significance not provided 2014-05-20 criteria provided, single submitter clinical testing p.Arg509Leu (CGC>CTC): c.1526 G>T in exon 11 of the FBN2 gene (NM_001999.3) The R509L variant has not been published as a mutation or reported as a benign polymorphism to our knowledge. The R509L variant was not observed 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. The R509L 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. This substitution occurs at a position that is conserved across species. In silico algorithms are not consistent in their predictions but at least two concur that R509L is probably damaging to the protein structure/function. Nevertheless, no missense mutations in nearby residues have been reported in association with CCA. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in TAAD
Ambry Genetics RCV000249767 SCV000319944 uncertain significance Cardiovascular phenotype 2015-08-07 criteria provided, single submitter clinical testing The p.R509L variant (also known as c.1526G>T), located in coding exon 11 of the FBN2 gene, results from a G to T substitution at nucleotide position 1526. The arginine at codon 509 is replaced by leucine, an amino acid with dissimilar properties. This variant was previously reported in the SNPDatabase as rs199587570,<span style="color:#000000"><span style="font-family:arial,sans-serif; font-size:10pt">but was not reported in population-based cohorts in the following databases:NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evident to date, the clinical significance of this variant remains unclear.

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