Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001000808 | SCV001157871 | uncertain significance | not specified | 2018-10-02 | criteria provided, single submitter | clinical testing | The EVC c.1652C>G; p.Pro551Arg variant (rs371682994), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found on a single chromosome in the Genome Aggregation Database, indicating it is not a common polymorphism. The proline at codon 551 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, due to limited information, the clinical significance of the p.Pro551Arg variant is uncertain at this time. |
| Labcorp Genetics |
RCV002549141 | SCV003249136 | uncertain significance | Ellis-van Creveld syndrome; Curry-Hall syndrome | 2022-07-26 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 551 of the EVC protein (p.Pro551Arg). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with EVC-related conditions. ClinVar contains an entry for this variant (Variation ID: 811140). 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 arginine 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. |