ClinVar Miner

Submissions for variant NM_024408.4(NOTCH2):c.4114C>T (p.Arg1372Trp)

gnomAD frequency: 0.00011  dbSNP: rs587778575
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001039672 SCV001203212 uncertain significance Hajdu-Cheney syndrome 2023-10-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1372 of the NOTCH2 protein (p.Arg1372Trp). This variant is present in population databases (rs587778575, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with NOTCH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 134974). 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 NOTCH2 protein function with a negative predictive value of 80%. 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.
Fulgent Genetics, Fulgent Genetics RCV002492436 SCV002776716 uncertain significance Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome 2022-02-18 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003133141 SCV003816004 uncertain significance not provided 2021-02-08 criteria provided, single submitter clinical testing
ITMI RCV000121724 SCV000085922 not provided not specified 2013-09-19 no assertion provided reference population

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