Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001330761 | SCV001522551 | likely pathogenic | Adams-Oliver syndrome 5 | 2020-03-17 | criteria provided, single submitter | clinical testing | This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Labcorp Genetics |
RCV001330761 | SCV003459881 | uncertain significance | Adams-Oliver syndrome 5 | 2021-12-18 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. ClinVar contains an entry for this variant (Variation ID: 1029477). This missense change has been observed in individual(s) with NOTCH1-related conditions (PMID: 29555671). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 718 of the NOTCH1 protein (p.Asn718Ser). |
| Gene |
RCV003324827 | SCV004030529 | uncertain significance | not provided | 2023-02-24 | criteria provided, single submitter | clinical testing | Reported in a proband with mitral valve stenosis and the mother with a ventricular septal defect (Szot et al., 2018); Functional studies demonstrate receptor maturation and signaling are similar to wildtype (Chapman et al., 2020); In silico analysis supports that this missense variant does not alter protein structure/function; However, in silico analysis supports a deleterious effect on splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29555671, 31813956) |
| Juno Genomics, |
RCV004796608 | SCV005416027 | uncertain significance | Aortic valve disease 1; Adams-Oliver syndrome 5 | criteria provided, single submitter | clinical testing | PM2_Supporting+PS2_Supporting+PS4_Supporting+PP2+PP4 |