Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001180130 | SCV001344997 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-07-26 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with tryptophan at codon 2282 of the FBN1 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in an individual affected with Marfan syndrome (PMID: 9338581) and in an individual suspected of having Marfan syndrome (PMID: 11700157). This variant has also been identified in 4/251282 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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. |
| Labcorp Genetics |
RCV001855423 | SCV002161052 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2021-01-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as 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. This variant has been observed in individual(s) with Marfan syndrome (PMID: 9338581, 11700157). ClinVar contains an entry for this variant (Variation ID: 549371). This variant is present in population databases (rs765205164, ExAC 0.03%). This sequence change replaces arginine with tryptophan at codon 2282 of the FBN1 protein (p.Arg2282Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. |
| All of Us Research Program, |
RCV000663905 | SCV004822424 | uncertain significance | Marfan syndrome | 2023-08-15 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with tryptophan at codon 2282 of the FBN1 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in an individual affected with Marfan syndrome (PMID: 9338581) and in an individual suspected of having Marfan syndrome (PMID: 11700157). This variant has also been identified in 4/251282 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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, |
RCV000663905 | SCV000787272 | uncertain significance | Marfan syndrome | 2017-11-07 | no assertion criteria provided | clinical testing |