Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Genomics, |
RCV000768033 | SCV000898860 | uncertain significance | Aortic valve disease 1; Adams-Oliver syndrome 5 | 2021-03-30 | criteria provided, single submitter | clinical testing | NOTCH1 NM_017617.5 exon 26 p.Arg1662Gln (c.4985G>A): This variant has not been reported in the literature and is not present in large control databases. This variant amino acid Glutamine (Gln) is present in several species, including multiple mammals, and it is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Invitae | RCV001869058 | SCV002142255 | uncertain significance | Adams-Oliver syndrome 5 | 2020-12-22 | criteria provided, single submitter | clinical testing | 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. 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. This variant has not been reported in the literature in individuals with NOTCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 625987). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces arginine with glutamine at codon 1662 of the NOTCH1 protein (p.Arg1662Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. |
Genome- |
RCV001869058 | SCV002553377 | uncertain significance | Adams-Oliver syndrome 5 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV002271020 | SCV002553378 | uncertain significance | Aortic valve disease 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV001702558 | SCV001927846 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001702558 | SCV001963700 | likely benign | not provided | no assertion criteria provided | clinical testing |