Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000688065 | SCV000815662 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2022-02-04 | criteria provided, single submitter | clinical testing | Studies have shown that disruption of this splice site results in skipping of exon 58, but is expected to preserve the integrity of the reading-frame (PMID: 30101859). ClinVar contains an entry for this variant (Variation ID: 567869). Disruption of this splice site has been observed in individual(s) with Marfan syndrome (PMID: 29357934, 30101859). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 58 of the FBN1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. For these reasons, this variant has been classified as Pathogenic. |
| 3billion | RCV002250681 | SCV002521414 | pathogenic | Marfan syndrome | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been reported to be associated with FBN1 related disorder (ClinVar ID: VCV000567869). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Human Genetics Bochum, |
RCV002250681 | SCV002758580 | likely pathogenic | Marfan syndrome | 2022-09-14 | criteria provided, single submitter | clinical testing | ACMG criteria used to clasify this variant: PVS1, PM2, PS4, PP3 |