ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.707C>T (p.Thr236Met) (rs537766290)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000655242 SCV000777172 uncertain significance Adams-Oliver syndrome 5 2017-08-21 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 236 of the NOTCH1 protein (p.Thr236Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. While this variant is present in population databases (rs537766290), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. 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.

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