Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000460089 | SCV000544870 | uncertain significance | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2021-05-19 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. This sequence change replaces glutamic acid with aspartic acid at codon 2742 of the FBN1 protein (p.Glu2742Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. It also falls at the last nucleotide of exon 65 of the FBN1 coding sequence. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change with uncertain impact on protein function and splicing. It has been classified as a Variant of Uncertain Significance. |