ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.6362G>A (p.Ser2121Asn) (rs761054017)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000467318 SCV000548933 uncertain significance Adams-Oliver syndrome 5 2016-09-28 criteria provided, single submitter clinical testing This sequence change replaces serine with asparagine at codon 2121 of the NOTCH1 protein (p.Ser2121Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine. This variant is present in population databases (rs761054017, ExAC 0.01%) 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. 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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