Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001124531 | SCV001283503 | uncertain significance | Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Prevention |
RCV003898122 | SCV004711971 | uncertain significance | NOTCH3-related condition | 2023-12-27 | criteria provided, single submitter | clinical testing | The NOTCH3 c.6334G>A variant is predicted to result in the amino acid substitution p.Gly2112Ser. This variant was reported in an individual with frontotemporal dementia (Table S2, Kim et al. 2018. PubMed ID: 30054184). Most CADASIL causing variants in the NOTCH3 gene result in the gain or loss of one or more cysteine residues in the extracellular domains of the protein. This variant does not involve a cysteine residue and is not located in an EGF-like domain in the protein. This variant is reported in 0.042% of alleles in individuals of East Asian descent in gnomAD, which is more common than expected for a pathogenic variant. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |