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

gnomAD frequency: 0.00005  dbSNP: rs778519094

Total submissions: 5

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	likely benign	Congenital contractural arachnodactyly	2023-09-12	criteria provided, single submitter	clinical testing
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)
Fulgent Genetics, Fulgent Genetics	RCV002483546	SCV002792766	uncertain significance	Congenital contractural arachnodactyly; Macular degeneration, early-onset	2021-10-29	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV002483546	SCV003919955	uncertain significance	Congenital contractural arachnodactyly; Macular degeneration, early-onset	2021-03-30	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.