Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000819517 | SCV000960182 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2018-11-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in FBN1 are known to be pathogenic (PMID: 17657824, 19293843). This variant has not been reported in the literature in individuals with FBN1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gly1316Argfs*10) in the FBN1 gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV003307545 | SCV004002648 | pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2023-03-19 | criteria provided, single submitter | clinical testing | The c.3945dupA pathogenic mutation, located in coding exon 31 of the FBN1 gene, results from a duplication of A at nucleotide position 3945, causing a translational frameshift with a predicted alternate stop codon (p.G1316Rfs*10). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with FBN1-related disease (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, 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. |