Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000803055 | SCV000942913 | pathogenic | Osteogenesis imperfecta type I | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly194Trpfs*14) in the COL1A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL1A1 are known to be pathogenic (PMID: 7942841, 9295084, 9443882). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL1A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 648346). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001008205 | SCV001167971 | pathogenic | not provided | 2018-06-20 | criteria provided, single submitter | clinical testing | The c.578dupC pathogenic variant in the COL1A1 gene causes a frameshift starting with codon Glycine 194, changes this amino acid to a Tryptophan residue and creates a premature Stop codon at position 14 of the new reading frame, denoted p.Gly194TrpfsX14. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.578dupC variant is not observed in large population cohorts (Lek et al., 2016). We classify this variant as pathogenic. |