ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.3245G>T (p.Arg1082Leu) (rs758471372)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000465938 SCV000548964 uncertain significance Adams-Oliver syndrome 5 2016-07-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 1082 of the NOTCH1 protein (p.Arg1082Leu). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is present in population databases (rs758471372, ExAC 0.003%) but has not been reported in the literature in individuals with a 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: "Damaging"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. It is not expected to cause disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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