Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000725797 | SCV000339476 | uncertain significance | not provided | 2016-02-11 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000725797 | SCV000573551 | uncertain significance | not provided | 2017-02-28 | criteria provided, single submitter | clinical testing | The H708Y variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The H708Y variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Missense variants in nearby residues (Y706H; V710G) have been reported in the Human Gene Mutation Database in association with GNE myopathy (Stenson et al., 2014); however, the H708Y substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
Invitae | RCV001206708 | SCV001378030 | uncertain significance | GNE myopathy; Sialuria | 2022-06-09 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 708 of the GNE protein (p.His708Tyr). This variant is present in population databases (rs527267621, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with GNE-related conditions. ClinVar contains an entry for this variant (Variation ID: 286153). 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 GNE 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. |
Natera, |
RCV001274361 | SCV001458427 | uncertain significance | GNE myopathy | 2020-09-16 | no assertion criteria provided | clinical testing |