Submissions for variant NM_017617.5(NOTCH1):c.1582G>A (p.Asp528Asn) (rs757988142)

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Total submissions: 2

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre of Medical Genetics, University of Antwerp	RCV000655250	SCV000747184	uncertain significance	Adams-Oliver syndrome 5	2017-12-01	criteria provided, single submitter	research
Invitae	RCV000655250	SCV000777180	uncertain significance	Adams-Oliver syndrome 5	2017-10-10	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid with asparagine at codon 528 of the NOTCH1 protein (p.Asp528Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs757988142, ExAC 0.003%). 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 C15"). 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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