Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000817656 | SCV000958233 | uncertain significance | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2021-12-23 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 660460). This missense change has been observed in individual(s) with clinical features of FBN1-related disease (Invitae). This variant is present in population databases (rs372404949, gnomAD 0.0009%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1134 of the FBN1 protein (p.Gly1134Arg). |
Gene |
RCV001772124 | SCV001993960 | uncertain significance | not provided | 2019-07-01 | 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). |
Ambry Genetics | RCV002453863 | SCV002612650 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-05-31 | criteria provided, single submitter | clinical testing | The p.G1134R variant (also known as c.3400G>A), located in coding exon 27 of the FBN1 gene, results from a G to A substitution at nucleotide position 3400. The glycine at codon 1134 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. |
Fulgent Genetics, |
RCV002487809 | SCV002781053 | 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 | 2021-10-29 | criteria provided, single submitter | clinical testing |