Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000483375 | SCV000573320 | uncertain significance | not provided | 2017-02-15 | criteria provided, single submitter | clinical testing | The Q1718L variant in the NEB gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Q1718L 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. This substitution occurs at a position where amino acids with similar properties to Glutamine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret Q1718L as a variant of uncertain significance. |
Labcorp Genetics |
RCV001834573 | SCV003002061 | uncertain significance | Nemaline myopathy 2 | 2022-07-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1718 of the NEB protein (p.Gln1718Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NEB-related conditions. ClinVar contains an entry for this variant (Variation ID: 423602). 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: "Not Available"; 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. |
Natera, |
RCV001834573 | SCV002077686 | uncertain significance | Nemaline myopathy 2 | 2021-01-25 | no assertion criteria provided | clinical testing |