Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000181521 | SCV000233824 | uncertain significance | not provided | 2022-10-06 | criteria provided, single submitter | clinical testing | Identified in a cohort of patients with mitral valve prolapse (MVP) in published literature (van Wijangaarden et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); 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); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32277046, 34826401, 12938084) |
Institute of Human Genetics, |
RCV002287381 | SCV002577842 | likely pathogenic | Abnormality of connective tissue | 2021-12-20 | criteria provided, single submitter | clinical testing | ACMG categories: PS1,PM2,PP5 |
Ambry Genetics | RCV002326983 | SCV002638408 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-08-08 | criteria provided, single submitter | clinical testing | The p.G1483R variant (also known as c.4447G>A), located in coding exon 35 of the FBN1 gene, results from a G to A substitution at nucleotide position 4447. The glycine at codon 1483 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
All of Us Research Program, |
RCV003996688 | SCV004826125 | uncertain significance | Marfan syndrome | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with arginine at codon 1483 of the FBN1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 FBN1-related disorders in the literature. 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. |