ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.3598G>A (p.Asp1200Asn) (rs544640305)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ITMI RCV000121678 SCV000085876 not provided not specified 2013-09-19 no assertion provided reference population
Invitae RCV000655259 SCV000777189 uncertain significance Adams-Oliver syndrome 5 2018-10-30 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 1200 of the NOTCH1 protein (p.Asp1200Asn). 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 (rs544640305, ExAC 0.09%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with NOTCH1-related disease. ClinVar contains an entry for this variant (Variation ID: 134928). 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: "Probably 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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