Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000434792 | SCV000533602 | uncertain significance | not provided | 2016-11-15 | criteria provided, single submitter | clinical testing | The S60C variant in the ALG14 gene has not been reported previously as a pathogenic variant, nor asa benign variant, to our knowledge. The S60C variant was not observed in approximately 6500individuals of European and African American ancestry in the NHLBI Exome Sequencing Project,indicating it is not a common benign variant in these populations. The S60C variant is anon-conservative amino acid substitution, which is likely to impact secondary protein structure asthese residues differ in polarity, charge, size and/or other properties. This substitution occurs at aposition that is conserved in mammals and in silico analysis predicts this variant is probably damagingto the protein structure/function. A missense variant in nearby residue (P65L) has been reported in the Human Gene Mutation Database in association with congenital myasthenic syndrome (Stenson et al.,2014), supporting the functional importance of this region of the protein. We interpret S60C as avariant of uncertain significance. |
Invitae | RCV000686830 | SCV000814366 | uncertain significance | Congenital myasthenic syndrome 15 | 2022-07-15 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 60 of the ALG14 protein (p.Ser60Cys). This variant is present in population databases (rs780277809, gnomAD 0.09%). 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: 390702). 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- |
RCV000686830 | SCV004049498 | uncertain significance | Congenital myasthenic syndrome 15 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003343824 | SCV004049499 | uncertain significance | Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003343825 | SCV004049500 | uncertain significance | Myopathy, epilepsy, and progressive cerebral atrophy | 2023-04-11 | criteria provided, single submitter | clinical testing |