Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002037924 | SCV002228109 | pathogenic | Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 | 2021-06-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with COL12A1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe2273Leufs*20) in the COL12A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL12A1 are known to be pathogenic (PMID: 24334604, 28973083). |
Gene |
RCV003229074 | SCV003926433 | likely pathogenic | not provided | 2023-05-08 | 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); Has not been previously published as pathogenic or benign to our knowledge |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV005238109 | SCV005887248 | pathogenic | Ullrich congenital muscular dystrophy 2 | 2025-01-14 | criteria provided, single submitter | clinical testing | Variant summary: COL12A1 c.6819delT (p.Phe2273LeufsX20) 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. The variant was absent in 248990 control chromosomes. To our knowledge, no occurrence of c.6819delT in individuals affected with Ullrich congenital muscular dystrophy 2 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1453491). Based on the evidence outlined above, the variant was classified as pathogenic. |