Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000668564 | SCV000793188 | likely pathogenic | Nemaline myopathy 2 | 2017-08-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000668564 | SCV002233948 | pathogenic | Nemaline myopathy 2 | 2024-07-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr8107Cysfs*75) 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 not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NEB-related conditions. ClinVar contains an entry for this variant (Variation ID: 553170). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003472102 | SCV004200217 | likely pathogenic | Arthrogryposis multiplex congenita 6 | 2024-02-07 | criteria provided, single submitter | clinical testing | |
| Juno Genomics, |
RCV000668564 | SCV005418223 | pathogenic | Nemaline myopathy 2 | criteria provided, single submitter | clinical testing | PM2_Supporting+PVS1+PP4 | |
| Broad Center for Mendelian Genomics, |
RCV005253049 | SCV005907785 | likely pathogenic | Nemaline myopathy | 2025-02-26 | criteria provided, single submitter | curation | The p.Tyr8072CysfsTer75 variant in NEB has not been previously reported in the literature in individuals with nemaline myopathy, but has been identified in 0.001% (1/74268) of African/African American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs2061157682). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID: 553170) and has been interpreted as pathogenic by Counsyl, Baylor Genetics, and Invitae. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 8072 and leads to a premature termination codon 75 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. 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 is likely pathogenic for autosomal recessive nemaline myopathy. ACMG/AMP Criteria applied: PVS1, PM2_supporting (Richards 2015). |