Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mayo Clinic Laboratories, |
RCV000516423 | SCV007136965 | pathogenic | not provided | 2025-10-18 | criteria provided, single submitter | clinical testing | PP1, PP2, PP3, PP4, PM1, PM2_supporting, PS4 |
| Labcorp Genetics |
RCV000516423 | SCV005838821 | pathogenic | not provided | 2025-04-10 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 54 of the NOTCH3 protein (p.Arg54Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (PMID: 19006080, 19242647, 26270344, 32277177). ClinVar contains an entry for this variant (Variation ID: 447791). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt NOTCH3 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
| Juno Genomics, |
RCV004796220 | SCV005418275 | likely pathogenic | Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1; Lateral meningocele syndrome; Myofibromatosis, infantile, 2 | criteria provided, single submitter | clinical testing | The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls.;Absent from controls (or at extremely low frequency if recessive) in Genome Aggregation Database, Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium.;Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.;Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc).;Patient's phenotype or family history is highly specific for a disease with a single genetic etiology. | |
| 3billion | RCV001253276 | SCV002318670 | pathogenic | Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 | 2022-03-22 | criteria provided, single submitter | clinical testing | Same or different nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000447791, PMID:11102981). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID: 26270344, 24139282, 32277177, 26002683, 11102981). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.803>=0.6). A missense variant is a common mechanism . It is not observed in the gnomAD v2.1.1 dataset. Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Institute of Human Genetics, |
RCV001253276 | SCV001428913 | likely pathogenic | Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 | 2017-12-27 | criteria provided, single submitter | clinical testing | |
| Athena Diagnostics | RCV000516423 | SCV000614231 | pathogenic | not provided | 2025-08-19 | criteria provided, single submitter | clinical testing | This variant alters a critical location within the protein, and is expected to severely affect function and cause disease. 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 of CADASIL. This variant appears to segregate with disease in at least one family, however, the available information does not rule out segregation due to chance. Greater than 90% of NOTCH3 pathogenic variants associated with CADASIL involve the gain or loss of a cysteine residue within the epidermal growth factor (EGF)-like repeat domain (PMID: 32457593, 20301673). |
| Genome |
RCV002508218 | SCV002818099 | not provided | Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy | no classification provided | phenotyping only | Variant classified as Pathogenic and reported on 02-03-2017 by Lab or GTR ID 1012. GenomeConnect-CureCADASIL assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. | |
| Genomics England Pilot Project, |
RCV001253276 | SCV001760443 | likely pathogenic | Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 | no assertion criteria provided | clinical testing |