Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000664008 | SCV004037323 | pathogenic | Marfan syndrome | 2023-09-28 | reviewed by expert panel | curation | The NM_000138.5 c.8051delinsTT variant in FBN1 is predicted to cause a frameshift resulting in a premature stop codon at position 2704 (p.Gly2684ValfsTer21), leading to an absent or disrupted protein product (PVS1). This variant was found in a pediatric proband with a systemic score of 7 and an aortic root Z-score >3, which is a highly specific phenotype for Marfan syndrome (PP4); this proband also carried another variant in FBN1, p.Tyr20Cys, which was considered a variant of unknown significance (internal data-Ghent University Hospital). This variant has been reported 1 time in ClinVar as a variant of uncertain significance (Variation ID: 549451). This variant is not present in gnomAD (PM2_sup; https://gnomad.broadinstitute.org/ version 2.1.1). In summary, this variant meets criteria to be classified as pathogenic for Marfan syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen FBN1 VCEP: PVS1, PM2_Supporting, PP4. |
Center for Medical Genetics Ghent, |
RCV000664008 | SCV000787393 | uncertain significance | Marfan syndrome | 2017-11-07 | no assertion criteria provided | clinical testing |