ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.787C>T (p.Arg263Trp) (rs151329128)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000195945 SCV000250264 uncertain significance not provided 2015-02-18 criteria provided, single submitter clinical testing p.Arg263Trp (CGG>TGG): c.787 C>T in exon 6 of the FBN2 gene (NM_001999.3) The R263W variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R263W variant was not observed with any significant frequency in approximately 6500 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 R263W 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 and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, no missense mutations in nearby residues have been reported, indicating this region of the protein may be tolerant of change. 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 TAADV2-1
Ambry Genetics RCV000618006 SCV000739044 uncertain significance Cardiovascular phenotype 2017-12-18 criteria provided, single submitter clinical testing The p.R263W variant (also known as c.787C>T), located in coding exon 6 of the FBN2 gene, results from a C to T substitution at nucleotide position 787. The arginine at codon 263 is replaced by tryptophan, an amino acid with dissimilar properties. Based on data from gnomAD, the T allele has an overall frequency of approximately 0.007% (20/276858) total alleles studied. The highest observed frequency was 0.069% (13/18864) of East Asian alleles. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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