Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Revvity Omics, |
RCV001784870 | SCV002019482 | pathogenic | not provided | 2019-12-26 | criteria provided, single submitter | clinical testing | |
Broad Center for Mendelian Genomics, |
RCV002544254 | SCV003761183 | likely pathogenic | Muscular dystrophy-dystroglycanopathy | 2023-01-24 | criteria provided, single submitter | curation | The p.Pro293fs variant in POMGNT1 has not been previously reported in the literature in individuals with POMGNT1-associated muscular dystrophy-dystroglycanopathy but has been identified in 0.003266% (1/30616) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs776248221). 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#: 1323487) and has been interpreted as pathogenic by PerkinElmer Genomics. This frameshift variant leads to a premature termination codon at amino acid position 333 which is predicted to lead to a truncated or absent protein.Loss of function of the POMGNT1 gene is an established disease mechanism in autosomal recessive POMGNT1-associated muscular dystrophy-dystroglycanopathy. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for POMGNT1-associated muscular dystrophy-dystroglycanopathy. ACMG/AMP Criteria applied: PVS1, PM2 (Richards 2015). |