ClinVar Miner

Submissions for variant NM_024408.4(NOTCH2):c.3878G>A (p.Arg1293His)

gnomAD frequency: 0.00009  dbSNP: rs201968231
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000594356 SCV000709645 uncertain significance not provided 2017-06-29 criteria provided, single submitter clinical testing
Invitae RCV001035605 SCV001198939 uncertain significance Hajdu-Cheney syndrome 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1293 of the NOTCH2 protein (p.Arg1293His). This variant is present in population databases (rs201968231, gnomAD 0.009%). 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: 502782). 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 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.
Fulgent Genetics, Fulgent Genetics RCV002491228 SCV002803884 uncertain significance Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome 2022-04-27 criteria provided, single submitter clinical testing

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