Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000734973 | SCV000863158 | uncertain significance | not provided | 2018-08-28 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001385021 | SCV001584729 | pathogenic | GNE myopathy; Sialuria | 2023-05-19 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 542 of the GNE protein (p.Pro542Ser). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro542 amino acid residue in GNE. Other variant(s) that disrupt this residue have been observed in individuals with GNE-related conditions (PMID: 16810679, 17718674), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GNE protein function. ClinVar contains an entry for this variant (Variation ID: 598553). This missense change has been observed in individual(s) with clinical features of GNE-related myopathy (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). |
Fulgent Genetics, |
RCV005049677 | SCV005682216 | likely pathogenic | GNE myopathy; Sialuria; Thrombocytopenia 12 with or without myopathy | 2024-02-16 | criteria provided, single submitter | clinical testing |