Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetics Institute, |
RCV001391264 | SCV001593213 | likely pathogenic | Corpus callosum, agenesis of; Abnormal cerebral cortex morphology; Colpocephaly | 2021-05-12 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001872000 | SCV002270875 | likely pathogenic | not provided | 2021-06-16 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with COL4A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1077129). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 6 of the COL4A1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL4A1 are known to be pathogenic (PMID: 23225343). |
3billion, |
RCV002250761 | SCV002521229 | pathogenic | Brain small vessel disease 1 with or without ocular anomalies | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Canonical splice site: predicted to alter splicing and 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. The variant has been reported to be associated with COL4A1 related disorder (ClinVar ID: VCV001077129). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
Institute of Human Genetics, |
RCV002250761 | SCV005423823 | pathogenic | Brain small vessel disease 1 with or without ocular anomalies | 2024-11-12 | criteria provided, single submitter | clinical testing | Criteria applied: PVS1,PS2,PS4_MOD,PM2_SUP |