Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000547129 | SCV000640931 | pathogenic | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 10 | 2017-08-11 | criteria provided, single submitter | clinical testing | This variant is an in-frame deletion of the genomic region encompassing exons 3-6 of the DOK7 gene. It preserves the integrity of the reading frame. While this deletion has not been reported in the literature in individuals with a DOK7-related disease, a similar deletion encompassing exons 3-5 (c.101_652del) has been reported in an individual with autosomal recessive congenital myasthenic syndrome. This individual was also reported to carry a second, pathogenic DOK7 variant (PMID: 18626973). Experimental studies have shown that deletion of exons 3-5 impairs the ability of DOK7 protein to phosphorylate MuSK due to the removal of key functional domains (PMID: 18626973). The same functional domains are removed by deletion of exons 3-6, which implies that this deletion will also impair protein function. Loss-of-function variants in DOK7 are known to cause autosomal recessive congenital myasthenia syndrome (PMID: 16917026, 18626973). For these reasons, this variant has been classified as Pathogenic. |