Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000517353 | SCV000614275 | pathogenic | not provided | 2020-12-14 | criteria provided, single submitter | clinical testing | This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. Assessment of experimental evidence suggests this variant results in abnormal protein function. Study showed this variant rescued stroke susceptibility phenotype in young notch 3 knock-out mice, but failed to rescue older mice suggesting it might be an age-dependent hypomorphic variant (PMID: 21555590). This variant alters a critical location within the protein, and is expected to severely affect function and cause disease. Greater than 90% of NOTCH3 pathogenic mutations associated with CADASIL involve the gain or loss of a cysteine residue within the epidermal growth factor (EGF)-like repeat domain (PMID: 32457593, 20301673). |
| MGZ Medical Genetics Center | RCV002289703 | SCV002579456 | pathogenic | Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 | 2021-08-17 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV000517353 | SCV004225105 | pathogenic | not provided | 2023-02-15 | criteria provided, single submitter | clinical testing | PP2, PP4, PM1, PM2, PS3, PS4 |