Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000181527 | SCV000233830 | uncertain significance | not provided | 2016-10-26 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the FBN1 gene. The T1529N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The T1529N variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved in mammals. Furthermore, missense variants in nearby residues (C1526Y, D1528N, R1528Y) have been reported in the Human Gene Mutation Database in association with Marfan syndrome (Stenson et al., 2014). Nevertheless, the T1529N variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Moreover, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Finally, T1529N does not affects a Cysteine residue within a calcium-binding EGF-like domain of the FBN1 gene, which represent the majority of pathogenic missense changes associated with Marfan syndrome (Collod-Beroud et al., 2003). Thus, this variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |
| Fulgent Genetics, |
RCV002478609 | SCV002782178 | 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 | 2021-12-04 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV003996690 | SCV004827399 | uncertain significance | Marfan syndrome | 2023-11-28 | criteria provided, single submitter | clinical testing |