Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Integrated Genetics/Laboratory Corporation of America | RCV000781652 | SCV000919864 | pathogenic | Nemaline myopathy | 2018-01-19 | criteria provided, single submitter | clinical testing | Variant summary: The NEB c.25241T>G (p.Leu8414X) variant results in a premature termination codon, predicted to cause a truncated or absent NEB protein due to nonsense mediated decay, which are commonly known mechanisms for disease.This variant was found in 1/218132 control chromosomes (gnomAD and publication controls) at a frequency of 0.0000046, which does not exceed the estimated maximal expected allele frequency of a pathogenic NEB variant (0.0035355). Multiple publications have cited the variant in affected compound heterozygote individuals with Nemaline Myopathy. The variant of interest has not, to our knowledge, been cited by clinical diagnostic laboratories. Taken together, this variant is classified as Pathogenic. |
| Invitae | RCV001214341 | SCV001386018 | pathogenic | Nemaline myopathy 2 | 2019-05-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu8414*) in the NEB gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs760200697, ExAC 0.005%). This variant has been reported in individuals affected with nemaline myopathy (PMID: 12207938, 25356970, 25205138). This variant is also known as p.L6523* in the literature. Loss-of-function variants in NEB are known to be pathogenic (PMID: 25205138). For these reasons, this variant has been classified as Pathogenic. |