ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.4027G>A (p.Ala1343Thr) (rs369654090)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000548273 SCV000659437 uncertain significance Adams-Oliver syndrome 5 2017-04-27 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1343 of the NOTCH1 protein (p.Ala1343Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs369654090, ExAC 0.03%) 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, 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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