ClinVar Miner

Submissions for variant NM_024408.4(NOTCH2):c.2142C>G (p.His714Gln)

gnomAD frequency: 0.00001  dbSNP: rs1553198250
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001997635 SCV002245249 uncertain significance Hajdu-Cheney syndrome 2021-08-12 criteria provided, single submitter clinical testing This sequence change replaces histidine with glutamine at codon 714 of the NOTCH2 protein (p.His714Gln). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with NOTCH2-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 NOTCH2 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.
Fulgent Genetics, Fulgent Genetics RCV002484821 SCV002790114 uncertain significance Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome 2021-11-05 criteria provided, single submitter clinical testing

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