Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001071071 | SCV001236355 | uncertain significance | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2019-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with proline at codon 780 of the FBN1 protein (p.Gln780Pro). The glutamine residue is moderately conserved and there is a moderate physicochemical difference between glutamine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FBN1-related conditions. 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"). 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. |
| Ambry Genetics | RCV005338561 | SCV006002752 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2025-01-27 | criteria provided, single submitter | clinical testing | The p.Q780P variant (also known as c.2339A>C), located in coding exon 19 of the FBN1 gene, results from an A to C substitution at nucleotide position 2339. The glutamine at codon 780 is replaced by proline, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |