Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center for Human Genetics, |
RCV000659399 | SCV000781210 | pathogenic | Stickler syndrome type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
| Clinical Genetics and Genomics, |
RCV001269590 | SCV001449684 | pathogenic | not provided | 2017-09-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001269590 | SCV001826466 | pathogenic | not provided | 2022-06-10 | 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); Reported in ClinVar as a pathogenic variant but additional evidence is not available (ClinVar Variant ID# 547258; ClinVar); This variant is associated with the following publications: (PMID: 10486316, 33726816) |
| 3billion | RCV000659399 | SCV002058635 | pathogenic | Stickler syndrome type 1 | 2022-01-03 | criteria provided, single submitter | clinical testing | Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000547258, PMID:10486316). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Invitae | RCV001269590 | SCV002240046 | pathogenic | not provided | 2021-07-22 | 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: 547258). This variant is also known as deletion of nt 22,620 (C) in E34. This premature translational stop signal has been observed in individual(s) with Stickler syndrome (PMID: 10486316). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Pro794Leufs*87) in the COL2A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL2A1 are known to be pathogenic (PMID: 20179744). |