ClinVar Miner

Submissions for variant NM_024408.4(NOTCH2):c.3430A>G (p.Ser1144Gly)

gnomAD frequency: 0.00003  dbSNP: rs143866883
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001988497 SCV002270153 uncertain significance Hajdu-Cheney syndrome 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 1144 of the NOTCH2 protein (p.Ser1144Gly). This variant is present in population databases (rs143866883, 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: 1488275). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 RCV002492260 SCV002800813 uncertain significance Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome 2021-10-21 criteria provided, single submitter clinical testing

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