Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000810432 | SCV000950630 | uncertain significance | Dilated cardiomyopathy 1J | 2025-01-27 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 139 of the EYA4 protein (p.Ser139Thr). This variant is present in population databases (rs146999911, gnomAD 0.05%). 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: 654464). 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. |
| Laboratory for Molecular Medicine, |
RCV000825758 | SCV000967220 | likely benign | not specified | 2018-12-19 | criteria provided, single submitter | clinical testing | The p.Ser139Thr variant in EYA4 is classified as likely benign because it has be en identified in 0.04% (12/24964) of African chromosomes by gnomAD (http://gnoma d.broadinstitute.org). ACMG/AMP criteria applied: BS1. |
| Gene |
RCV001585740 | SCV001818360 | uncertain significance | not provided | 2022-07-19 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002332663 | SCV002628086 | uncertain significance | Cardiovascular phenotype | 2024-10-25 | criteria provided, single submitter | clinical testing | The p.S139T variant (also known as c.415T>A), located in coding exon 6 of the EYA4 gene, results from a T to A substitution at nucleotide position 415. The serine at codon 139 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |