Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002315077 | SCV000739395 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-02-23 | criteria provided, single submitter | clinical testing | The p.R20L variant (also known as c.59G>T), located in coding exon 1 of the NOTCH1 gene, results from a G to T substitution at nucleotide position 59. The arginine at codon 20 is replaced by leucine, an amino acid with dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. This position was not covered in the ESP. This amino acid position is not well conserved on limited sequence alignment. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV001855279 | SCV002152556 | uncertain significance | Adams-Oliver syndrome 5 | 2021-09-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with leucine at codon 20 of the NOTCH1 protein (p.Arg20Leu). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and leucine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 520031). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Genome- |
RCV001855279 | SCV002554025 | uncertain significance | Adams-Oliver syndrome 5 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV002270877 | SCV002554026 | uncertain significance | Aortic valve disease 1 | 2022-03-15 | criteria provided, single submitter | clinical testing |