ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.7250C>T (p.Pro2417Leu) (rs370652630)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000233982 SCV000290307 uncertain significance Adams-Oliver syndrome 5 2018-05-23 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 2417 of the NOTCH1 protein (p.Pro2417Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs370652630, ExAC 0.006%). This variant has not been reported in the literature in individuals with NOTCH1-related disease. ClinVar contains an entry for this variant (Variation ID: 241165). 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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