Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001813007 | SCV001473134 | uncertain significance | not provided | 2020-06-22 | criteria provided, single submitter | clinical testing | The EVC2 c.3419G>A; p.Arg1140His variant (rs779684008), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is only observed on three alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The arginine at codon 1140 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Arg1140His variant is uncertain at this time. |
| Labcorp Genetics |
RCV002542979 | SCV003273907 | uncertain significance | Ellis-van Creveld syndrome; Curry-Hall syndrome | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 1140 of the EVC2 protein (p.Arg1140His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with EVC2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |