Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002027823 | SCV002310241 | uncertain significance | Dilated cardiomyopathy 1J | 2024-11-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 356 of the EYA4 protein (p.Arg356Gln). This variant is present in population databases (rs762144530, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with EYA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1521211). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt EYA4 protein function with a negative predictive value of 80%. 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. |
| Gene |
RCV002290841 | SCV002578687 | uncertain significance | not provided | 2022-04-07 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Fulgent Genetics, |
RCV002479816 | SCV002785165 | uncertain significance | Dilated cardiomyopathy 1J; Autosomal dominant nonsyndromic hearing loss 10 | 2021-08-09 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004044735 | SCV005021547 | uncertain significance | Cardiovascular phenotype | 2023-11-22 | criteria provided, single submitter | clinical testing | The p.R356Q variant (also known as c.1067G>A), located in coding exon 11 of the EYA4 gene, results from a G to A substitution at nucleotide position 1067. The arginine at codon 356 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |