Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002418574 | SCV002678437 | pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2021-07-12 | criteria provided, single submitter | clinical testing | The c.8059_8060delGT pathogenic mutation, located in coding exon 64 of the FBN1 gene, results from a deletion of two nucleotides between nucleotide positions 8059 and 8060, causing a translational frameshift with a predicted alternate stop codon (p.V2687Ffs*17). A similar variant, reported as c.8056_8057delTG, has been detected in an individual with aortic dilation and systemic features of Marfan syndrome (Zarate YA et al. Genet Med. 2016 Apr;18(4):356-63). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Invitae | RCV003769011 | SCV004595360 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-06-05 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 870214). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val2687Phefs*17) in the FBN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FBN1 are known to be pathogenic (PMID: 17657824, 19293843). |
| Clinical Molecular Genetics Laboratory, |
RCV001089766 | SCV001192856 | pathogenic | Marfan syndrome | 2017-04-21 | no assertion criteria provided | clinical testing |