Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002311080 | SCV000319860 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2015-06-30 | criteria provided, single submitter | clinical testing | The p.R1164C variant (also known as c.3490C>T), located in coding exon 27 of the FBN2 gene, results from a C to T substitution at nucleotide position 3490. The arginine at codon 1164 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is conserved in all available species, except opossum. 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 variant remains unclear. |
Gene |
RCV001764238 | SCV001989967 | uncertain significance | not provided | 2020-11-24 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 264140; Landrum et al., 2016) |
Invitae | RCV001859459 | SCV002153145 | uncertain significance | Congenital contractural arachnodactyly | 2021-05-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 1164 of the FBN2 protein (p.Arg1164Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with FBN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 264140). This variant is not present in population databases (ExAC no frequency). |
Ce |
RCV001764238 | SCV004161338 | uncertain significance | not provided | 2023-07-01 | criteria provided, single submitter | clinical testing | FBN2: PM2, PP3 |