Submissions for variant NM_000138.5(FBN1):c.3337+1dup

dbSNP: rs1566909762

Total submissions: 1

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	RCV002053877	SCV002320679	likely pathogenic	Ectopia lentis 1, isolated, autosomal dominant; Marfan syndrome; MASS syndrome; Stiff skin syndrome; Weill-Marchesani syndrome 2, dominant; Acromicric dysplasia; Geleophysic dysplasia 2; Progeroid and marfanoid aspect-lipodystrophy syndrome	2021-11-03	criteria provided, single submitter	clinical testing	FBN1 NM_000138.4 intron 26 c.3337+1dup: This variant has not been reported in the literature and is not present in large control databases. Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is a duplication of 1 nucleotide at the canonical splice site which is predicted to shift the canonical splice site 1 nucleotide position downstream. This is likely to cause the incorporation of 1 additional base into the exonic coding sequences, leading to a frameshift and creation of a premature stop codon downstream, resulting in an absent or abnormal protein. Loss of function variants are a known mechanism of disease for this gene (Dietz 2017 PMID: 20301510). In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant is classified as likely pathogenic.