ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.8498G>A (p.Arg2833His) (rs753753954)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197185 SCV000250259 uncertain significance not provided 2012-11-20 criteria provided, single submitter clinical testing p.Arg2833His (CGT>CAT): c.8498 G>A in exon 65 of the FBN2 gene (NM_001999.3) The Arg2833His variant in the FBN2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Although Arg2833His results in a conservative amino acid substitution of one positively charged amino acid with another, the substitution occurs at a position that is conserved across species. In silico analysis predicts Arg2833His is possibly damaging to the protein structure/function. The NHLBI ESP Exome Variant Server reports Arg2833His was not observed in approximately 6,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Nevertheless, no mutations in nearby codons have been reported in association with congenital contractural arachnodactyly or an FBN2-related disorder. With the clinical and molecular information available at this time, we cannot definitively determine if Arg2833His is a disease-causing mutation or a rare benign variant. This variant was found in TAAD
Ambry Genetics RCV000254164 SCV000320225 uncertain significance Cardiovascular phenotype 2015-09-07 criteria provided, single submitter clinical testing The p.R2833H variant (also known as c.8498G>A), located in coding exon 65 of the FBN2 gene, results from a G to A substitution at nucleotide position 8498. The arginine at codon 2833 is replaced by histidine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis.<span style="color:black; font-family:arial,sans-serif; font-size:10pt">Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.

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