ClinVar Miner

Submissions for variant NC_000015.9:g.(?_48426485)_(48730124_?)del

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001941947 SCV002233105 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2020-11-25 criteria provided, single submitter clinical testing 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). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with FBN1-related conditions. This variant is a gross deletion of the genomic region encompassing exon(s) 51-66 of the FBN1 gene. The 5' boundary is likely confined to intron 50. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to alter mRNA translation or result in a truncated protein product.

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