Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000217424 | SCV000271765 | uncertain significance | not specified | 2017-10-24 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Arg113Cys var iant in ESPN has been previously reported by our laboratory in the heterozygous state in 2 individuals with hearing loss; however, a variant affecting the remai ning copy of ESPN was not identified in either of them. This variant has been id entified in 0.04% (123/275670) of total chromosomes including 0.1% (40/34420) of Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.br oadinstitute.org/; dbSNP rs143577178). Although this variant has been seen in th e general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analysis suggest that the p.Arg113Cys variant may impact the protein, though this information is not predi ctive enough to determine pathogenicity. In summary, while the clinical signific ance of the p.Arg113Cys variant is uncertain, its frequency in the general popul ation suggests that it is more likely to be benign. ACMG/AMP Criteria applied: B S1_Support, PP3 (Richards 2015). |
| Labcorp Genetics |
RCV001853451 | SCV002287873 | uncertain significance | not provided | 2022-07-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 113 of the ESPN protein (p.Arg113Cys). This variant is present in population databases (rs143577178, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with nonsyndromic deafness (PMID: 30344259). ClinVar contains an entry for this variant (Variation ID: 228670). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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. |
| Revvity Omics, |
RCV001853451 | SCV003832275 | uncertain significance | not provided | 2019-07-12 | criteria provided, single submitter | clinical testing | |
| Institute of Human Genetics, |
RCV004816368 | SCV005072910 | uncertain significance | Retinal dystrophy | 2022-01-01 | criteria provided, single submitter | clinical testing |