Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001189501 | SCV001356809 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-11-03 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with asparagine at codon 521 of the FBN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with FBN1-related disorders in the literature. This variant has been identified in 4/251338 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. |
| Ambry Genetics | RCV001189501 | SCV002704979 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-02-25 | criteria provided, single submitter | clinical testing | The p.S521N variant (also known as c.1562G>A), located in coding exon 12 of the FBN1 gene, results from a G to A substitution at nucleotide position 1562. The serine at codon 521 is replaced by asparagine, an amino acid with highly similar properties, and is located in the cb EGF-like #03 domain. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002484033 | SCV002789699 | 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 | 2021-09-16 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003770135 | SCV004581311 | likely benign | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2022-12-14 | criteria provided, single submitter | clinical testing |