Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000608987 | SCV000712821 | likely pathogenic | Walker-Warburg congenital muscular dystrophy | 2017-03-02 | criteria provided, single submitter | clinical testing | The p.Phe162SerfsX10 (NM007171.3 c.485delT) variant in POMT1 has not been report ed in individuals with POMT1-related muscular dystrophy-dystroglycanopathies. Th is variant has been identified in 1/8254 of European chromosomes by the NHLBI Ex ome Sequencing Project (http://evs.gs.washington.edu/EVS). Although this variant has been seen in the general population, its frequency is low enough to be cons istent with a recessive carrier frequency. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 162 and leads to a premature termination codon 10 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Biallelic loss of function of the POMT1 gene has been associated with POMT1-related muscu lar dystrophy-dystroglycanopathies. In summary, although additional studies are required to fully establish a null effect, the p.Phe162SerfsX10 variant is likel y pathogenic for POMT1-related muscular dystrophy-dystroglycanopathies in an aut osomal recessive manner based upon its predicted impact on protein function. |
| Gene |
RCV002510929 | SCV002820860 | pathogenic | not provided | 2022-07-14 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Identified in the heterozygous state through genome sequencing in published literature; however, no clinical information or information on whether a second variant was identified was provided (Ceyhan-Birsoy et al., 2019; Hou et al., 2020); This variant is associated with the following publications: (PMID: 31980526, 30609409) |
| Labcorp Genetics |
RCV002529346 | SCV003300869 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy | 2023-04-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 505535). This variant has not been reported in the literature in individuals affected with POMT1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Phe162Serfs*10) in the POMT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POMT1 are known to be pathogenic (PMID: 12369018, 15637732, 16575835). |
| Baylor Genetics | RCV003471973 | SCV004204058 | pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 | 2024-02-15 | criteria provided, single submitter | clinical testing |