Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000191079 | SCV000245474 | 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 [A380fs] 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 |
| Labcorp Genetics |
RCV001223983 | SCV001396154 | likely pathogenic | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 10 | 2022-07-26 | criteria provided, single submitter | clinical testing | This sequence change results in a frameshift in the DOK7 gene (p.Gly496Serfs*26). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 9 amino acid(s) of the DOK7 protein and extend the protein by 16 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This frameshift has been observed in individual(s) with clinical features of 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. ClinVar contains an entry for this variant (Variation ID: 209148). This variant disrupts a region of the DOK7 protein in which other variant(s) (p.Gly496Val) have been observed in individuals with DOK7-related conditions (PMID: 22661499). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |