Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000470418 | SCV000544840 | uncertain significance | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2016-12-27 | criteria provided, single submitter | clinical testing | A different variant with the same protein effect (c.7978A>C, p.Ser2660Arg) has been observed in two related individuals diagnosed with Marfan syndrome using the Ghent criteria, findings that are highly specific for Marfan syndrome (PMID: 16835936). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role 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 do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FBN1-related disease. This sequence change replaces serine with arginine at codon 2660 of the FBN1 protein (p.Ser2660Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine. |
Blueprint Genetics | RCV000788115 | SCV000927122 | uncertain significance | not provided | 2017-01-13 | criteria provided, single submitter | clinical testing | |
Center for Medical Genetics Ghent, |
RCV000664003 | SCV000787387 | uncertain significance | Marfan syndrome | 2017-11-07 | no assertion criteria provided | clinical testing |