ClinVar Miner

Submissions for variant NM_000435.3(NOTCH3):c.2208C>G (p.Asp736Glu)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV005178091 SCV005807680 uncertain significance not provided 2024-09-25 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 736 of the NOTCH3 protein (p.Asp736Glu). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with early onset Alzheimer disease (PMID: 31182772). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt NOTCH3 protein function with a negative predictive value of 95%. 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.

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