Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000667046 | SCV000791437 | likely pathogenic | Nemaline myopathy 2 | 2017-05-23 | criteria provided, single submitter | clinical testing | |
| Integrated Genetics/Laboratory Corporation of America | RCV000781654 | SCV000919866 | likely pathogenic | Nemaline myopathy | 2018-05-21 | criteria provided, single submitter | clinical testing | Variant summary: NEB c.24458_24461dupAGAT (p.Met8154IlefsX13) 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 (eg. c.24559C>T, p.Arg8187X; c.24632_24633delCT, p.Pro8211fsX4; c.25241T>G, p.Leu8414X). The variant allele was found at a frequency of 8.7e-06 in 230296 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in NEB causing Nemaline Myopathy 2 (8.7e-06 vs 3.50e-03), allowing no conclusion about variant significance. The variant, c.24458_24461dupAGAT, has been reported in the literature in individuals affected with unspecified form of NM (Lehtokari_2014). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 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. |