ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.5697C>A (p.Asn1899Lys)

dbSNP: rs747229390
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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 RCV001991231 SCV002266927 uncertain significance Adams-Oliver syndrome 5 2021-08-03 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 1899 of the NOTCH1 protein (p.Asn1899Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. 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. 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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