ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.7058G>A (p.Arg2353His) (rs775905979)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000473008 SCV000553184 uncertain significance Congenital contractural arachnodactyly 2016-06-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 2353 of the FBN2 protein (p.Arg2353His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs775905979, ExAC 0.003%) but has not been reported in the literature in individuals with a FBN2-related disease. 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001001161 SCV001158312 uncertain significance not specified 2019-03-26 criteria provided, single submitter clinical testing The FBN2 c.7058G>A; p.Arg2353His variant (rs775905979), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 411818). This variant is only observed on 3 out of 250,820 allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The arginine at codon 2353 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Arg2353His variant is uncertain at this time.

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