Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002326343 | SCV002606180 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2019-06-06 | criteria provided, single submitter | clinical testing | The p.F1105L variant (also known as c.3315C>G), located in coding exon 26 of the FBN1 gene, results from a C to G substitution at nucleotide position 3315. The phenylalanine at codon 1105 is replaced by leucine, an amino acid with highly similar properties, and is located in the cbEGF-like #12 domain. 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. |
| Labcorp Genetics |
RCV003102354 | SCV003473985 | uncertain significance | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2022-01-01 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs770232184, gnomAD 0.002%). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1105 of the FBN1 protein (p.Phe1105Leu). |