Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000169034 | SCV000220184 | likely pathogenic | Nemaline myopathy 2 | 2014-03-22 | criteria provided, single submitter | literature only | |
| Integrated Genetics/Laboratory Corporation of America | RCV000589380 | SCV000697826 | pathogenic | Nemaline myopathy | 2017-02-23 | criteria provided, single submitter | clinical testing | Variant summary: The NEB c.2784delT (p.Asp929Ilefs) 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. Truncations downstream of this position have been classified as likely pathogenic/pathogenic by our laboratory (e.g. c.11164C>T (p.Arg3722X), c.24218C>A (p.Ser8073X), and c.24559C>T (p.Arg8187X)). This variant is absent in 112170 control chromosomes. A publication cites the variant in an affected individual indicated to have severe NM, who was a compound heterozygote for the variant (paternally inherited) and a four-copy gain (maternally inherited). In addition, a clinical diagnostic laboratory classified the variant as "likely pathogenic", without evidence to independently evaluation. Taken together, the variant of interest has been classified as "pathogenic." |
| Invitae | RCV000169034 | SCV000944751 | pathogenic | Nemaline myopathy 2 | 2018-10-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp929Ilefs*28) in the NEB gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another NEB variant in an individual affected with nemaline myopathy (PMID: 26197980). ClinVar contains an entry for this variant (Variation ID: 188731). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. Loss-of-function variants in NEB are known to be pathogenic (PMID: 25205138). For these reasons, this variant has been classified as Pathogenic. |