Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001844648 | SCV002103835 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy | 2022-02-18 | criteria provided, single submitter | clinical testing | Variant summary: POMT1 c.2106_2116del11 (p.Val703LeufsX24) 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 not been observed at our laboratory but have been reported in association with Walker-Warburg Syndrome and other POMT1 associated phenotypes in the HGMD/LOVD databases. The variant was absent in 232498 control chromosomes. c.2106_2116del11 has been reported in the literature as a homozygous genotype in at-least one individual affected with Walker-Warburg Syndrome (example, Beltran-Valero de Bernabe_2002) and has subsequently been cited by numerous authors without primary evidence (example, Balci_2005, Currier_2005, Akasaka-Manya_2006, can Reeuwijk_2006, Akasaka-Manya_2004). These data indicate that the variant may be associated with disease. To our knowledge, no variant specific experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV002034732 | SCV002146747 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy | 2023-08-08 | criteria provided, single submitter | clinical testing | This variant disrupts a region of the POMT1 protein in which other variant(s) (p.Asp723Glyfs*8) have been determined to be pathogenic (PMID: 12369018, 16575835, 17559086, 22323514, 24304607, 24491487). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1343631). This variant has not been reported in the literature in individuals affected with POMT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val703Leufs*24) in the POMT1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 45 amino acid(s) of the POMT1 protein. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003475106 | SCV004204047 | likely pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 | 2024-01-21 | criteria provided, single submitter | clinical testing |