Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000689140 | SCV000816780 | likely pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-03-10 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FBN1 protein function. ClinVar contains an entry for this variant (Variation ID: 568701). This missense change has been observed in individuals with ectopia lentis and Marfan syndrome (PMID: 20564469, 24161884; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 634 of the FBN1 protein (p.Ser634Pro). |
Institute of Human Genetics, |
RCV001800851 | SCV002047384 | uncertain significance | Pes planus; Arachnodactyly; Mitral valve prolapse; Lens luxation; Aortic aneurysm | 2021-12-13 | criteria provided, single submitter | clinical testing | ACMG categories: PM2,PP3,BP1 |