Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000535696 | SCV000659496 | uncertain significance | Adams-Oliver syndrome 5 | 2021-08-13 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with aspartic acid at codon 2515 of the NOTCH1 protein (p.Glu2515Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
Ambry Genetics | RCV002315061 | SCV000739466 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-02-14 | criteria provided, single submitter | clinical testing | The p.E2515D variant (also known as c.7545G>T), located in coding exon 34 of the NOTCH1 gene, results from a G to T substitution at nucleotide position 7545. The glutamic acid at codon 2515 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. 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 alteration remains unclear. |
Gene |
RCV001764632 | SCV001989205 | uncertain significance | not provided | 2021-02-24 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Genome- |
RCV000535696 | SCV002555189 | uncertain significance | Adams-Oliver syndrome 5 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV002270713 | SCV002555190 | uncertain significance | Aortic valve disease 1 | 2022-03-15 | criteria provided, single submitter | clinical testing |