ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.4238G>A (p.Arg1413His) (rs371068504)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000248136 SCV000320436 uncertain significance Cardiovascular phenotype 2015-11-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient or conflicting evidence,In silico models in agreement (benign)
Fulgent Genetics,Fulgent Genetics RCV000766060 SCV000897516 uncertain significance Aortic valve disorder; Adams-Oliver syndrome 5 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000471799 SCV000548959 uncertain significance Adams-Oliver syndrome 5 2017-07-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1413 of the NOTCH1 protein (p.Arg1413His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs371068504, ExAC 0.009%). This variant has not been reported in the literature in individuals with NOTCH1-related disease. ClinVar contains an entry for this variant (Variation ID: 264469). 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 and their clinical significance is uncertain. 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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