Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001221280 | SCV001393312 | uncertain significance | Cutis laxa, autosomal recessive, type 1B | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with tryptophan at codon 427 of the EFEMP2 protein (p.Arg427Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with EFEMP2-related conditions. 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. 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 | RCV002379835 | SCV002694612 | uncertain significance | Cardiovascular phenotype | 2020-12-07 | criteria provided, single submitter | clinical testing | The p.R427W variant (also known as c.1279C>T), located in coding exon 10 of the EFEMP2 gene, results from a C to T substitution at nucleotide position 1279. The arginine at codon 427 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. 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 alteration remains unclear. |