Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV000513502 | SCV000608857 | uncertain significance | not provided | 2017-05-01 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000513502 | SCV000708124 | uncertain significance | not provided | 2017-05-02 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000817319 | SCV000957872 | uncertain significance | Vici syndrome | 2022-10-25 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2389 of the EPG5 protein (p.Leu2389Val). This variant is present in population databases (rs199602966, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with EPG5-related conditions. ClinVar contains an entry for this variant (Variation ID: 444432). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt EPG5 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. |
Center for Genomics, |
RCV000817319 | SCV001468414 | uncertain significance | Vici syndrome | 2021-03-30 | criteria provided, single submitter | clinical testing | EPG5 NM_020964.2 exon 41 p.Leu2389Val (c.7165T>G): This variant has not been reported in the literature but is present in 0.1% (152/128640) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/18-43438592-A-C?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:444432). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. Of note, splice prediction tools suggest that this variant may affect splicing. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Ambry Genetics | RCV002527409 | SCV003526201 | uncertain significance | Inborn genetic diseases | 2021-12-06 | criteria provided, single submitter | clinical testing | The c.7165T>G (p.L2389V) alteration is located in exon 41 (coding exon 41) of the EPG5 gene. This alteration results from a T to G substitution at nucleotide position 7165, causing the leucine (L) at amino acid position 2389 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |