ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.4835G>A (p.Gly1612Asp)

dbSNP: rs1223921509
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001799354 SCV002043529 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-05-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005095168 SCV005762410 uncertain significance Adams-Oliver syndrome 5 2024-08-31 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1612 of the NOTCH1 protein (p.Gly1612Asp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1329311). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt NOTCH1 protein function with a negative predictive value of 80%. 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.

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