Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV004582944 | SCV005064023 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2022-11-09 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant affects a cysteine residue 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). A similar copy number variant has been observed in individual(s) with Marfan syndrome (PMID: 30286810). This variant is a gross deletion of the genomic region encompassing exon(s) 56 of the FBN1 gene. This variant would be expected to be in-frame, preserving the integrity of the reading frame. |