Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Diagnostics Services |
RCV001003494 | SCV001161699 | uncertain significance | GNE myopathy | 2020-02-04 | criteria provided, single submitter | clinical testing | The c.469C>A variant is not present in publicly available databases like 1000 Genomes, EVS, ExAC, gnomAD and dbSNP. The variant is also not present in our in-house exome database. The variant was not reported earlier to OMIM, ClinVar or HGMD databases. In-silico pathogenicity prediction programs SIFT, Polyphen2, MutationTaster2, CADD etc. predicted this variant as likely deleterious. However no functional studies were performed to check for the effect of the variant on mRNA and protein. The variant was observed in compound heterozygous state with an another pathogenic variant c.2086G>A (ClinVar Accession ID: VCV000006028.6). Due to lack of enough evidence the variant has been classified as uncertain significance. |
| Invitae | RCV002549214 | SCV003507922 | uncertain significance | GNE myopathy; Sialuria | 2023-03-24 | criteria provided, single submitter | clinical testing | 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. 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: 812702). This variant has not been reported in the literature in individuals affected with GNE-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 188 of the GNE protein (p.His188Asn). |