Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002510384 | SCV002819622 | likely pathogenic | Congenital myasthenic syndrome | 2022-12-16 | criteria provided, single submitter | clinical testing | Variant summary: DOK7 c.1370_1446del77 (p.Glu457GlyfsX36) causes a frameshift in exon 7 (i.e. in the last exon of the encoded protein sequence) and results in a premature termination codon. This variant is not predicted to cause nonsense mediated decay, but is expected to disrupt the last part of the 504 amino acid long protein, replacing it with a shorter, incorrect sequence. The variant was absent in 211364 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1370_1446del77 in individuals affected with Congenital Myasthenic Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. However, frameshift variants downstream from this variant (i.e. Glu457) have been reported in individuals affected with Congenital Myasthenic Syndrome (HGMD). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |