Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000535311 | SCV000630262 | uncertain significance | Congenital contractural arachnodactyly | 2023-11-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 2620 of the FBN2 protein (p.Gly2620Glu). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with FBN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 458780). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 | RCV002413466 | SCV002670933 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-11-12 | criteria provided, single submitter | clinical testing | The c.7859_7860delGGinsAA variant (also known as p.G2620E), located in coding exon 62 of the FBN2 gene, results from an in-frame deletion of GG and insertion of AA at nucleotide positions 7859 to 7860. This results in the substitution of the glycine residue for a glutamic acid residue at codon 2620, an amino acid with similar properties, and is located in the cbEGF-like #42 domain. This amino acid substitution (p.G2620E, described as c.7859G>A) was reported in a severe scoliosis cohort; however, clinical details were limited (Buchan JG et al. Hum Mol Genet, 2014 Oct;23:5271-82). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |