Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000150679 | SCV000198038 | uncertain significance | not specified | 2014-07-29 | criteria provided, single submitter | clinical testing | The Pro88Arg variant in EYA4 has not been previously reported in individuals wit h hearing loss or in large population studies. Computational prediction tools an d conservation analyses do not provide strong support for or against an impact t o the protein. In summary, the clinical significance of the Pro88Arg variant is uncertain. |
| Labcorp Genetics |
RCV000699690 | SCV000828413 | uncertain significance | Dilated cardiomyopathy 1J | 2025-01-12 | 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 88 of the EYA4 protein (p.Pro88Arg). This variant is present in population databases (rs727503050, 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: 163443). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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 | RCV002453484 | SCV002739696 | uncertain significance | Cardiovascular phenotype | 2024-01-16 | criteria provided, single submitter | clinical testing | The p.P88R variant (also known as c.263C>G), located in coding exon 4 of the EYA4 gene, results from a C to G substitution at nucleotide position 263. The proline at codon 88 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is well 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. |
| Center for Genomics, |
RCV003224172 | SCV003919925 | uncertain significance | Dilated cardiomyopathy 1J; Autosomal dominant nonsyndromic hearing loss 10 | criteria provided, single submitter | clinical testing | EYA4 NM_004100.4 exon 5 p.Pro88Arg (c.263C>G): This variant has not been reported in the literature but is present in 0.01% (5/35438) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/6-133769303-C-G). This variant is present in ClinVar (Variation ID:163443). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. | |
| Gene |
RCV004812303 | SCV005437298 | uncertain significance | not provided | 2024-06-12 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000150679 | SCV005886838 | uncertain significance | not specified | 2025-02-03 | criteria provided, single submitter | clinical testing |