ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.7298T>C (p.Phe2433Ser) (rs201493851)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000822987 SCV000963819 uncertain significance Adams-Oliver syndrome 5 2018-11-29 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with serine at codon 2433 of the NOTCH1 protein (p.Phe2433Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. This variant is present in population databases (rs201493851, ExAC 0.06%). This variant has not been reported in the literature in individuals with NOTCH1-related conditions. 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 and their clinical significance is uncertain. 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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