Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000589559 | SCV000619688 | uncertain significance | not provided | 2022-12-14 | criteria provided, single submitter | clinical testing | Has been reported in a patient with a connective tissue disorder phenotype (Renner et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Does not affect a cysteine residue within a calcium-binding EGF-like domain or a TGF-binding protein domain of the FBN1 gene; 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); This variant is associated with the following publications: (PMID: 30675029) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589559 | SCV000695430 | uncertain significance | not provided | 2017-02-15 | criteria provided, single submitter | clinical testing | Variant summary: The FBN1 c.1211C>G (p.Pro404Arg) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 120,304 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available. |
| Labcorp Genetics |
RCV001857995 | SCV002108715 | likely benign | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2024-01-12 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004003620 | SCV004823069 | uncertain significance | Marfan syndrome | 2023-09-17 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with arginine at codon 404 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 been reported in two related individuals affected with hereditary connective tissue disorder (PMID: 30675029) and in an individual affected with ascending aortic aneurysm (Weerakkody 2017, doctoral thesis, Imperial College London). 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. |