ClinVar Miner

Submissions for variant NM_024408.4(NOTCH2):c.6056G>A (p.Arg2019Gln)

gnomAD frequency: 0.00004  dbSNP: rs201446896
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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) RCV000177810 SCV000229744 uncertain significance not provided 2015-04-23 criteria provided, single submitter clinical testing
Invitae RCV001852200 SCV002110352 uncertain significance Hajdu-Cheney syndrome 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2019 of the NOTCH2 protein (p.Arg2019Gln). This variant is present in population databases (rs201446896, 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: 196923). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV002485161 SCV002776690 uncertain significance Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome 2022-02-18 criteria provided, single submitter clinical testing

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