ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.1510C>T (p.Arg504Cys) (rs752071569)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000559630 SCV000659375 uncertain significance Adams-Oliver syndrome 5 2017-04-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 504 of the NOTCH1 protein (p.Arg504Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs752071569, ExAC 0.002%) 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes 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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