Submissions for variant NM_173660.5(DOK7):c.1236C>A (p.Cys412Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003781026	SCV004569600	pathogenic	Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 10	2022-12-13	criteria provided, single submitter	clinical testing	This premature translational stop signal has been observed in individual(s) with congenital myasthenic syndrome (PMID: 28716243). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. 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.Pro486Argfs*15) have been determined to be pathogenic (PMID: 29118959). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Cys412*) in the DOK7 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 93 amino acid(s) of the DOK7 protein.
Baylor Genetics	RCV004573305	SCV005059598	pathogenic	Fetal akinesia deformation sequence 3	2024-01-01	criteria provided, single submitter	clinical testing