ClinVar Miner

Submissions for variant NM_024408.4(NOTCH2):c.1978A>G (p.Met660Val)

gnomAD frequency: 0.00001  dbSNP: rs1447605154
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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 RCV001230219 SCV001402693 uncertain significance Hajdu-Cheney syndrome 2023-07-25 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 660 of the NOTCH2 protein (p.Met660Val). 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. 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. ClinVar contains an entry for this variant (Variation ID: 957268). 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).
Fulgent Genetics, Fulgent Genetics RCV002480755 SCV002788246 uncertain significance Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome 2022-05-04 criteria provided, single submitter clinical testing

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