ClinVar Miner

Submissions for variant NM_020964.3(EPG5):c.7165T>G (p.Leu2389Val)

gnomAD frequency: 0.00053  dbSNP: rs199602966
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000513502 SCV000608857 uncertain significance not provided 2017-05-01 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000513502 SCV000708124 uncertain significance not provided 2017-05-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp 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, Ann and Robert H. Lurie Children's Hospital of Chicago 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.

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