Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000792152 | SCV000931430 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2019-06-27 | criteria provided, single submitter | clinical testing | This variant is an in-frame deletion of the genomic region encompassing exon 49 of the FBN1 gene. It preserves the integrity of the reading frame. This variant has been observed in several individuals affected with Marfan syndrome (PMID: 25907466, Invitae). This variant affects cysteine residues in the EGF-like, TGFBP or hybrid motif domains of FBN1. Cysteine residues are believed to be involved in intramolecular disulfide bridges and have been shown to be important for FBN1 protein structure (PMID: 16905551, 19349279). In addition, missense substitutions affecting cysteine residues within these domains are significantly overrepresented among patients with Marfan syndrome (PMID: 16571647, 17701892). For these reasons, this variant has been classified as Pathogenic. |