Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002311151 | SCV000320280 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-10-19 | criteria provided, single submitter | clinical testing | The p.T1035I variant (also known as c.3104C>T), located in coding exon 19 of the NOTCH1 gene, results from a C to T substitution at nucleotide position 3104. The threonine at codon 1035 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly 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 variant remains unclear. |
Fulgent Genetics, |
RCV000764817 | SCV000895968 | uncertain significance | Aortic valve disease 1; Adams-Oliver syndrome 5 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001854991 | SCV002206694 | uncertain significance | Adams-Oliver syndrome 5 | 2022-06-13 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NOTCH1 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 264380). This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1035 of the NOTCH1 protein (p.Thr1035Ile). |
Genome- |
RCV001854991 | SCV002553512 | uncertain significance | Adams-Oliver syndrome 5 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV002270180 | SCV002553513 | uncertain significance | Aortic valve disease 1 | 2022-03-15 | criteria provided, single submitter | clinical testing |