Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000474427 | SCV000544929 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2024-03-01 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 886 of the FBN1 protein (p.Pro886Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with FBN1-related conditions (PMID: 33483584; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 406356). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
| Color Diagnostics, |
RCV005401445 | SCV006061554 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-11-05 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with leucine at codon 886 of the FBN1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual with definitive or suspected Marfan syndrome (PMID: 33483584). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Center for Medical Genetics Ghent, |
RCV000663564 | SCV000786875 | uncertain significance | Marfan syndrome | 2017-11-07 | no assertion criteria provided | clinical testing |