ClinVar Miner

Submissions for variant NM_024408.4(NOTCH2):c.3916G>A (p.Asp1306Asn)

gnomAD frequency: 0.00010  dbSNP: rs116408209
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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) RCV000733846 SCV000861947 uncertain significance not provided 2018-06-23 criteria provided, single submitter clinical testing
Invitae RCV001855791 SCV002187728 uncertain significance Hajdu-Cheney syndrome 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1306 of the NOTCH2 protein (p.Asp1306Asn). This variant is present in population databases (rs116408209, gnomAD 0.007%). 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: 597664). 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%. 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 RCV002493360 SCV002784354 uncertain significance Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome 2022-05-06 criteria provided, single submitter clinical testing

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