Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000476977 | SCV000548917 | benign | Adams-Oliver syndrome 5 | 2024-01-08 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000523567 | SCV000621033 | uncertain significance | not provided | 2018-05-15 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the NOTCH1 gene. The R879Q variant has been reported as a variant of uncertain significance in one patient with aortopathy (Yang et al., 2016). This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The R879Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved across species and where glutamine (Q) is present as the wild type in at least one species. Finally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
Genome- |
RCV000476977 | SCV002553539 | uncertain significance | Adams-Oliver syndrome 5 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV002270495 | SCV002553540 | uncertain significance | Aortic valve disease 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002451109 | SCV002740000 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-06-03 | criteria provided, single submitter | clinical testing | The p.R879Q variant (also known as c.2636G>A), located in coding exon 17 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 2636. The arginine at codon 879 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in a congenital heart defect cohort (Kerstjens-Frederikse WS et al. Genet Med, 2016 09;18:914-23). 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. |
Mayo Clinic Laboratories, |
RCV000523567 | SCV004225189 | uncertain significance | not provided | 2022-10-11 | criteria provided, single submitter | clinical testing | BP4, PP2 |
ARUP Laboratories, |
RCV000523567 | SCV004563226 | uncertain significance | not provided | 2023-04-26 | criteria provided, single submitter | clinical testing | The NOTCH1 c.2636G>A; p.Arg879Gln variant (rs368011392) is reported in the literature in an individual affected with hypoplastic left heart syndrome (Kerstjens-Frederikse 2016). This variant is reported in ClinVar (Variation ID: 409039) and is found in the general population with an overall allele frequency of 0.0091% (25/274,500 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.213). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Kerstjens-Frederikse WS et al. Cardiovascular malformations caused by NOTCH1 mutations do not keep left: data on 428 probands with left-sided CHD and their families. Genet Med. 2016 Sep;18(9):914-23. PMID: 26820064. |