ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.5987C>T (p.Thr1996Met)

gnomAD frequency: 0.00001  dbSNP: rs773137647
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000798259 SCV000937864 uncertain significance Adams-Oliver syndrome 5 2018-07-31 criteria provided, single submitter clinical testing 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. 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. This variant has not been reported in the literature in individuals with NOTCH1-related disease. This variant is present in population databases (rs773137647, ExAC 0.003%). This sequence change replaces threonine with methionine at codon 1996 of the NOTCH1 protein (p.Thr1996Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine.

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