ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.5494C>T (p.Arg1832Cys) (rs778519094)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000576804 SCV000678228 uncertain significance Congenital contractural arachnodactyly 2017-08-01 criteria provided, single submitter clinical testing FBN2 NM_001999.3 exon43 p.Arg1832Cys (c.5494C>T): This variant has not been reported in the literature but is present in 2/24032 African individuals in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs778519094). Evolutionary conservation 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.
Invitae RCV000576804 SCV000948916 uncertain significance Congenital contractural arachnodactyly 2019-12-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1832 of the FBN2 protein (p.Arg1832Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs778519094, ExAC 0.006%). This variant has not been reported in the literature in individuals with FBN2-related disease. ClinVar contains an entry for this variant (Variation ID: 487469). 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.
GeneDx RCV001551500 SCV001772022 uncertain significance not provided 2021-02-01 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 487469; Landrum et al., 2016)

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