Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001187017 | SCV001353674 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-03-03 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with leucine at codon 1009 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 affected with left ventricular non‐compaction (PMID: 30471092). 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. |
| Labcorp Genetics |
RCV001225327 | SCV001397603 | uncertain significance | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-05-26 | 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 1009 of the FBN1 protein (p.Pro1009Leu). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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: 925193). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. This variant is not present in population databases (gnomAD no frequency). |
| Fulgent Genetics, |
RCV002484022 | SCV002792225 | uncertain significance | Ectopia lentis 1, isolated, autosomal dominant; Marfan syndrome; MASS syndrome; Stiff skin syndrome; Weill-Marchesani syndrome 2, dominant; Acromicric dysplasia; Geleophysic dysplasia 2; Progeroid and marfanoid aspect-lipodystrophy syndrome | 2021-07-26 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004008652 | SCV004814838 | uncertain significance | Marfan syndrome | 2023-05-23 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with leucine at codon 1009 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 affected with left ventricular non-compaction (PMID: 30471092). 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. |
| Breakthrough Genomics, |
RCV004695131 | SCV005193792 | uncertain significance | not provided | criteria provided, single submitter | not provided |