ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.1885A>G (p.Asn629Asp) (rs863223554)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197851 SCV000250162 uncertain significance not provided 2015-08-12 criteria provided, single submitter clinical testing p.Asn629Asp (AAT>GAT): c.1885 A>G in exon 14 of the FBN2 gene (NM_001999.3) The Asn629Asp variant in the FBN2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Asn629Asp was not observed 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. Asn629Asp results in a semi-conservative amino acid substitution of neutral, polar Asparagine with a negatively-charged Aspartic acid at a position that is highly conserved across species. Consequently, in silico analysis predicts Asn629Asp is damaging to the protein structure/function. However, missense mutations in nearby residues have not been reported, indicating this region of the FBN2 protein may tolerate change. With the clinical and molecular information available at this time, we cannot definitively determine if Asn629Asp is a disease-causing mutation or a rare benign variant. . This variant was found in TAAD
Ambry Genetics RCV000252268 SCV000319661 uncertain significance Cardiovascular phenotype 2017-12-12 criteria provided, single submitter clinical testing The p.N629D variant (also known as c.1885A>G), located in coding exon 14 of the FBN2 gene, results from an A to G substitution at nucleotide position 1885. The asparagine at codon 629 is replaced by aspartic acid, an amino acid with highly similar properties, and is located in the cbEGF-like #06 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.
Invitae RCV001207170 SCV001378510 uncertain significance Congenital contractural arachnodactyly 2019-08-23 criteria provided, single submitter clinical testing This sequence change replaces asparagine with aspartic acid at codon 629 of the FBN2 protein (p.Asn629Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FBN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 213280). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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