ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.5605G>T (p.Ala1869Ser) (rs200603539)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000226317 SCV000290290 uncertain significance Adams-Oliver syndrome 5 2016-02-24 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 1869 of the NOTCH1 protein (p.Ala1869Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs200603539, ExAC 0.06%) 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this is a rare missense change that is not predicted to affect protein function or cause disease. However, the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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