ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.6397C>A (p.Pro2133Thr)

dbSNP: rs61733294
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001205231 SCV001376472 uncertain significance Adams-Oliver syndrome 5 2023-05-01 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. 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. ClinVar contains an entry for this variant (Variation ID: 936436). This variant is present in population databases (rs61733294, gnomAD 0.003%). This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2133 of the NOTCH1 protein (p.Pro2133Thr).
GeneDx RCV001546821 SCV001766408 uncertain significance not provided 2020-06-05 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; 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
Genome-Nilou Lab RCV001205231 SCV002553305 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002271192 SCV002553306 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing

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