Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000191080 | SCV000245475 | pathogenic | Congenital myasthenic syndrome 10 | 2014-06-13 | criteria provided, single submitter | clinical testing | This frameshift variant is categorized as deleterious according to ACMG guidelines (PMID:18414213) and was found once in our laboratory in trans with another frameshift variant [G496fs] in a 19-year-old male with congenital weakness, hypotonia, short stature, failure to thrive, ptosis with ophthalmoplegia, spinal curvature, scoliosis, bilateral vocal cord paralysis, partial paralysis of left side |
| Gene |
RCV000281028 | SCV000330694 | pathogenic | not provided | 2023-12-05 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26633545) |
| Labcorp Genetics |
RCV000641538 | SCV000763180 | pathogenic | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 10 | 2023-08-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the DOK7 protein in which other variant(s) (p.Cys412*, p.Gln460*, p.Gly479Hisfs*13) have been determined to be pathogenic (PMID: 20012313, 20458068, 28716243). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 209149). This premature translational stop signal has been observed in individual(s) with congenital myasthenic syndrome (PMID: 26633545; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs776704789, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Ala380Glyfs*27) in the DOK7 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 125 amino acid(s) of the DOK7 protein. |
| Baylor Genetics | RCV003468880 | SCV004194046 | pathogenic | Fetal akinesia deformation sequence 3 | 2023-04-13 | criteria provided, single submitter | clinical testing |