Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000674087 | SCV000799361 | likely pathogenic | Nemaline myopathy 2 | 2018-04-17 | criteria provided, single submitter | clinical testing | |
| Integrated Genetics/Laboratory Corporation of America | RCV001194218 | SCV001363577 | likely pathogenic | Nemaline myopathy | 2019-01-14 | criteria provided, single submitter | clinical testing | Variant summary: NEB c.20659C>T (p.Arg6887X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.21076C>T (p.Arg7026X), c.24407_24410dupTGTT (p.Leu8137fsX18), c.24559C>T (p.Arg8187X)). The variant allele was found at a frequency of 7.2e-06 in 275868 control chromosomes (gnomAD). c.20659C>T has been reported in the literature in a family affected with Nemaline Myopathy 2 (Lehtokari 2014). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |