Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000825517 | SCV000966830 | likely pathogenic | Knobloch syndrome | 2018-04-12 | criteria provided, single submitter | clinical testing | The p.Arg1081X variant in COL18A1 has not been previously reported in individual s with Knobloch syndrome, but has been identified in 1/1622 East Asian chromosom es by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs771752014). Although this variant has been seen in the general populati on, its frequency is low enough to be consistent with a recessive carrier freque ncy. This nonsense variant leads to a premature termination codon at position 10 81, which is predicted to lead to a truncated or absent protein. Loss of functio n of the COL18A1 gene is an established disease mechanism in autosomal recessive Knobloch syndrome. In summary, although additional studies are required to full y establish its clinical significance, this variant is likely pathogenic. ACMG/A MP Criteria applied: PVS1_Strong; PM2. |
| Labcorp Genetics |
RCV001869266 | SCV002202679 | pathogenic | not provided | 2022-08-09 | 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: 666965). This variant has not been reported in the literature in individuals affected with COL18A1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Arg1078*) in the COL18A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL18A1 are known to be pathogenic (PMID: 12415512, 25456301). |