Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001183523 | SCV001349280 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-11-04 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with leucine at codon 510 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 not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 3/282682 chromosomes 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 |
RCV001366835 | SCV001563152 | uncertain significance | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 510 of the FBN1 protein (p.Ser510Leu). This variant is present in population databases (rs776942896, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 923073). 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%. 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. |
| Gene |
RCV001593315 | SCV001816287 | uncertain significance | not provided | 2019-09-17 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Although located in a calcium-binding EGF-like domain of the FBN1 gene, it does not affect a cysteine residue within this domain; cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN1-related disorders (Collod-Beroud et al., 2003) |
| Fulgent Genetics, |
RCV002484002 | SCV002782553 | 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 | 2021-08-19 | criteria provided, single submitter | clinical testing |