Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000697148 | SCV000825744 | pathogenic | Nemaline myopathy 2 | 2024-12-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp542Ilefs*15) in the NEB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NEB are known to be pathogenic (PMID: 25205138). This variant is present in population databases (rs772366030, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with nemaline myopathy (PMID: 16917880, 25205138). This variant is also known as g.37528delT. ClinVar contains an entry for this variant (Variation ID: 575054). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001192839 | SCV001361228 | pathogenic | Nemaline myopathy | 2022-08-05 | criteria provided, single submitter | clinical testing | Variant summary: NEB c.1623delT (p.Asp542IlefsX15) 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. The variant allele was found at a frequency of 4e-06 in 249060 control chromosomes. c.1623delT has been reported in the literature in individuals affected with Nemaline Myopathy 2 in the compound heterozygous state (Lehtokari_2014, Wu_2018, Wang_2020). These data indicate that the variant is likely to be associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV004569340 | SCV005056264 | pathogenic | Arthrogryposis multiplex congenita 6 | 2024-03-12 | criteria provided, single submitter | clinical testing |