ClinVar Miner

Submissions for variant NM_173660.5(DOK7):c.513C>T (p.Gly171=) (rs775583136)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493977 SCV000582447 likely pathogenic not provided 2019-01-16 criteria provided, single submitter clinical testing The c.513C>T variant in the DOK7 gene has previously been reported along with a pathogenic variant in two individuals with congenital myasthenic syndrome (Cossins et al., 2012). Functional studies using exon trapping suggest c.513C>T causes an in-frame deletion of the last 7 amino acids in exon 4 of the DOK7 gene (Cossins et al., 2012). This variant creates a cryptic splice donor site for intron 4, located 21bp upstream of the natural site . The c.513C>T variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a nucleotide position that is not conserved across species. The c.513C>T variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Baylor Miraca Genetics Laboratories, RCV000679965 SCV000807399 pathogenic Myasthenia, limb-girdle, familial 2017-09-01 criteria provided, single submitter clinical testing This mutation has been previously reported as disease-causing and was found once in our laboratory in trans with another pathogenic mutation in a 13-year-old female with motor delays, hypotonia, neurogenic myopathy, fatigue, ptosis, joint contractures. The c.513C>T mutation, which does not affect amino acid translation, was shown to affect mRNA splicing in the literature.

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