Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV001254698 | SCV001430764 | likely pathogenic | Muscular dystrophy, limb-girdle, autosomal recessive 23 | 2020-05-29 | criteria provided, single submitter | research | The heterozygous p.Asp1127ValfsTer47 variant in TRAPPC11 was identified by our study, in the compound heterozygous state, in 1 individual with limb girdle muscular dystrophy (PMID: 31575891). This variant was absent from large population studies. In vitro functional studies provide some evidence that the p.Asp1127ValfsTer47 variant may impact protein function (PMID: 31575891). However, these types of assays may not accurately represent biological function. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1127 and leads to a premature termination codon 47 amino acids downstream. This termination codon occurs within the last exon and is more likely to escape nonsense mediated decay (NMD) and result in a truncated protein. The presence of this variant in combination with a reported pathogenic variant, and in an individual with limb-girdle muscular dystrophy increases the likelihood that the p.Asp1127ValfsTer47 variant is pathogenic (PMID: 31575891). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PM3, PS3_moderate (Richards 2015). |