Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002041389 | SCV002110546 | uncertain significance | GNE myopathy; Sialuria | 2021-08-15 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 692 of the GNE protein (p.Asn692Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs765173992, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with GNE-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
Revvity Omics, |
RCV003132548 | SCV003815080 | uncertain significance | not provided | 2021-08-17 | criteria provided, single submitter | clinical testing | |
Neuberg Centre For Genomic Medicine, |
RCV003448421 | SCV004176692 | uncertain significance | GNE myopathy | 2023-03-01 | criteria provided, single submitter | clinical testing | The missense c.1982A>G (p.Asn661Ser) variant in GNE gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Asn661Ser variant has allele frequency 0.0004% is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid change p.Asn661Ser in GNE is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Asn at position 661 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS). |