Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000433819 | SCV000523320 | uncertain significance | not provided | 2018-11-05 | criteria provided, single submitter | clinical testing | The G47V variant in the ALG14 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The G47V variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G47V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret G47V as a variant of uncertain significance. |
Invitae | RCV001318009 | SCV001508696 | uncertain significance | Congenital myasthenic syndrome 15 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with valine at codon 47 of the ALG14 protein (p.Gly47Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs139758313, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with ALG14-related conditions. ClinVar contains an entry for this variant (Variation ID: 383072). 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. |
Genome- |
RCV001318009 | SCV004049503 | uncertain significance | Congenital myasthenic syndrome 15 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003343818 | SCV004049504 | uncertain significance | Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003343819 | SCV004049505 | uncertain significance | Myopathy, epilepsy, and progressive cerebral atrophy | 2023-04-11 | criteria provided, single submitter | clinical testing |