Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000559298 | SCV000641808 | uncertain significance | Vici syndrome | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 511 of the EPG5 protein (p.His511Asp). This variant is present in population databases (rs762634619, gnomAD 0.2%). 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: 466237). 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 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. |
Gene |
RCV001569770 | SCV001793913 | uncertain significance | not provided | 2020-06-25 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function Observed on 0.1725% (61/35368 alleles) from individuals of Latino background in the ExAC dataset, which is greater than expected for this disorder (Lek et al., 2016) Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002526143 | SCV003705311 | likely benign | Inborn genetic diseases | 2022-06-29 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Prevention |
RCV004751590 | SCV005350632 | likely benign | EPG5-related disorder | 2024-05-28 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |