Total submissions: 18
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000479282 | SCV000567322 | pathogenic | not provided | 2022-01-04 | 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; This variant is associated with the following publications: (PMID: 21937992, 28041643, 25456301, 23667181, 19160445, 20979194, 31415705, 12415512, 33238767, 31896775, 32178553, 28950998, 32581362, 29977801) |
Blueprint Genetics | RCV001074487 | SCV001240074 | pathogenic | Retinal dystrophy | 2017-09-15 | criteria provided, single submitter | clinical testing | |
Centre for Mendelian Genomics, |
RCV001198207 | SCV001369077 | pathogenic | Glaucoma, primary closed-angle | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Pathogenic. |
Labcorp Genetics |
RCV000479282 | SCV001416967 | pathogenic | not provided | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu1172Valfs*72) 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). This variant is present in population databases (rs398122391, gnomAD 0.04%). This premature translational stop signal has been observed in individuals with Knobloch syndrome (PMID: 19390655, 21862674, 23667181, 29977801). It has also been observed to segregate with disease in related individuals. This variant is also known as p.Leu1587Valfs*72. ClinVar contains an entry for this variant (Variation ID: 65410). For these reasons, this variant has been classified as Pathogenic. |
Institute of Medical Genetics and Applied Genomics, |
RCV000479282 | SCV001447309 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000479282 | SCV001501806 | pathogenic | not provided | 2023-06-01 | criteria provided, single submitter | clinical testing | COL18A1: PVS1, PM2, PM3 |
Greenwood Genetic Center Diagnostic Laboratories, |
RCV000479282 | SCV002051613 | pathogenic | not provided | 2021-03-03 | criteria provided, single submitter | clinical testing | PVS1, PM2, PM3 |
Genetic Services Laboratory, |
RCV000479282 | SCV002064455 | pathogenic | not provided | 2018-04-18 | criteria provided, single submitter | clinical testing | |
DASA | RCV000055632 | SCV002107162 | pathogenic | Knobloch syndrome | 2022-03-05 | criteria provided, single submitter | clinical testing | The c.4054_4055delCT;p.(Leu1355Valfs*72) is a null frameshift variant (NMD) in the COL18A1 gene and predicts alteration of the nonsense-mediate decay - NMD is present in a relevant exon to the transcript - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 65410; PMID: 29977801; PMID: 21862674; PMID: 23667181; PMID: 19390655) - PS4. The variant is present at low allele frequencies population databases (rs398122391 – gnomAD 0.002961%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. In summary, the currently available evidence indicates that the variant is pathogenic. |
Fulgent Genetics, |
RCV002504954 | SCV002812897 | pathogenic | Glaucoma, primary closed-angle; Knobloch syndrome 1 | 2022-03-29 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235024 | SCV003934783 | pathogenic | Knobloch syndrome 1 | 2023-05-04 | criteria provided, single submitter | clinical testing | Variant summary: COL18A1 c.3523_3524delCT (p.Leu1175ValfsX72) 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 allele was found at a frequency of 0.0003 in 194886 control chromosomes. c.3523_3524delCT has been reported in the literature in individuals affected with Knobloch Syndrome 1 (example: Villanueva-Mendoza_2021). These data indicate that the variant is likely associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 34828430). 12 clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic (n=11) or likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic. |
Clinical Genetics Laboratory, |
RCV000479282 | SCV005199173 | pathogenic | not provided | 2022-06-21 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000055632 | SCV000038936 | pathogenic | Knobloch syndrome | 2010-11-01 | no assertion criteria provided | literature only | |
NIHR Bioresource Rare Diseases, |
RCV000504900 | SCV000598896 | likely pathogenic | Macular dystrophy | 2015-01-01 | no assertion criteria provided | research | |
NIHR Bioresource Rare Diseases, |
RCV000505165 | SCV000598897 | likely pathogenic | Retinitis pigmentosa | 2015-01-01 | no assertion criteria provided | research | |
Molecular Genetics Laboratory, |
RCV000055632 | SCV000924662 | pathogenic | Knobloch syndrome | 2017-12-13 | no assertion criteria provided | research | |
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000479282 | SCV001952203 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000479282 | SCV001973916 | pathogenic | not provided | no assertion criteria provided | clinical testing |