Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000667317 | SCV000791748 | pathogenic | Nemaline myopathy 2 | 2017-05-23 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000667317 | SCV000949478 | pathogenic | Nemaline myopathy 2 | 2024-02-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg8218Serfs*9) 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 (rs755863625, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with nemaline myopathy (PMID: 25205138). ClinVar contains an entry for this variant (Variation ID: 552108). 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, |
RCV001194217 | SCV001363576 | pathogenic | Nemaline myopathy | 2022-01-12 | criteria provided, single submitter | clinical testing | Variant summary: NEB c.24654_24655delAG (p.Arg8218SerfsX9) 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 1.2e-05 in 240344 control chromosomes (gnomAD). c.24654_24655delAG has been reported in the literature in individuals affected with Nemaline Myopathy (Lehtokari_2014). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV003465475 | SCV004200057 | pathogenic | Arthrogryposis multiplex congenita 6 | 2024-02-12 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV001194217 | SCV004848921 | likely pathogenic | Nemaline myopathy | 2023-02-02 | criteria provided, single submitter | clinical testing | The p.Arg8218SerfsX9 in NEB has not been previously reported in individuals with nemaline myopathy and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 8218 and leads to a premature termination codon 9 amino acids downstream. Loss of function of the NEB gene is an established disease mechanism in autosomal recessive nemaline myopathy. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive nemaline myopathy. ACMG/AMP Criteria applied: PVS1, PM2_Supporting. |
| Fulgent Genetics, |
RCV005019118 | SCV005650352 | pathogenic | Nemaline myopathy 2; Arthrogryposis multiplex congenita 6 | 2024-03-23 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000667317 | SCV001459163 | pathogenic | Nemaline myopathy 2 | 2020-09-16 | no assertion criteria provided | clinical testing |