ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.7115G>A (p.Arg2372Gln) (rs373119531)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000529611 SCV000659490 uncertain significance Adams-Oliver syndrome 5 2018-02-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 2372 of the NOTCH1 protein (p.Arg2372Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs373119531, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with NOTCH1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV000620680 SCV000739507 uncertain significance Cardiovascular phenotype 2017-11-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000529611 SCV000782577 uncertain significance Adams-Oliver syndrome 5 2017-01-19 criteria provided, single submitter clinical testing

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