ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.3481G>A (p.Glu1161Lys) (rs1554123065)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000549680 SCV000630220 uncertain significance Congenital contractural arachnodactyly 2017-01-25 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1161 of the FBN2 protein (p.Glu1161Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with contractural arachnodactyly in a single family (PMID: 19006240). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000765799 SCV000897189 uncertain significance Congenital contractural arachnodactyly; Macular degeneration, early-onset 2018-10-31 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000765799 SCV000898706 uncertain significance Congenital contractural arachnodactyly; Macular degeneration, early-onset 2018-10-24 criteria provided, single submitter clinical testing FBN2 NM_001999.3 exon27 p.Glu1161Lys (c.3481G>A): This variant has been reported in the literature in 1 individual with congenital contractural arachnodactyly, segregating with disease in 4 affected family members (Callewaert 2009 PMID:19006240). Additionally, this variant is not present in large control databases. This variant is present in ClinVar (Variation ID: 458759). Evolutionary consevation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001090286 SCV001245734 uncertain significance not provided 2019-11-01 criteria provided, single submitter clinical testing

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