ClinVar Miner

Submissions for variant NM_024408.4(NOTCH2):c.2321A>G (p.Asn774Ser)

dbSNP: rs2526252133
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003023746 SCV003318103 uncertain significance Hajdu-Cheney syndrome 2022-11-01 criteria provided, single submitter clinical testing 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. This variant has not been reported in the literature in individuals affected with NOTCH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 774 of the NOTCH2 protein (p.Asn774Ser).
Ambry Genetics RCV003170894 SCV003884707 uncertain significance Inborn genetic diseases 2023-01-10 criteria provided, single submitter clinical testing The c.2321A>G (p.N774S) alteration is located in exon 14 (coding exon 14) of the NOTCH2 gene. This alteration results from a A to G substitution at nucleotide position 2321, causing the asparagine (N) at amino acid position 774 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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