ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.7418G>T (p.Arg2473Leu) (rs28763925)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000199839 SCV000250312 uncertain significance not specified 2017-06-05 criteria provided, single submitter clinical testing The R2473L variant in the FBN2 gene has been reported as a suspected benign" variant in two patients with featuresof Marfan syndrome, one of whom also harbored a variant in the SMAD3 gene (Wooderchak-Donahue et al., 2015).While the R2473L variant has been identified in other individuals referred for TAAD/Marfan syndrome testing atGeneDx, observation in these individuals, for whom segregation data is lacking, is not sufficient to determine theabsolute pathogenicity of this variant. R2473L was observed in 16/6,612 (0.24%) alleles from individuals ofEuropean (Finnish) ancestry in the Exome Aggregation Consortium (Lek et al., 2016). Although located within acalcium-binding EGF-like domain of FBN2, the R2473L variant does not affect a Cysteine residue. Cysteinesubstitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changesassociated with with CCA (Collod-Beroud et al., 2003; Frederic et al., 2009). Nevertheless, the R2473L variant is anon-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differin polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals,and in silico analysis predicts R2473L is damaging to the protein structure/function."
Illumina Clinical Services Laboratory,Illumina RCV000366798 SCV000452548 likely benign Congenital contractural arachnodactyly 2016-06-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000620447 SCV000738977 likely benign Cardiovascular phenotype 2019-03-13 criteria provided, single submitter clinical testing Subpopulation frequency in support of benign classification
Invitae RCV000366798 SCV000754901 likely benign Congenital contractural arachnodactyly 2020-06-21 criteria provided, single submitter clinical testing

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