ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3281T>C (p.Ile1094Thr) (rs1338658857)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000660606 SCV000782722 pathogenic Niemann-Pick disease type C1 2017-08-11 criteria provided, single submitter clinical testing
Invitae RCV000660606 SCV000826598 uncertain significance Niemann-Pick disease type C1 2018-05-04 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 1094 of the NPC1 protein (p.Ile1094Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in a family affected with Niemann-Pick type C (PMID: 12408188). 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 disruptive, 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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