ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3205A>G (p.Met1069Val) (rs1567946736)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000693173 SCV000821030 uncertain significance Niemann-Pick disease type C1 2018-07-16 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 1069 of the NPC1 protein (p.Met1069Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NPC1-related disease. 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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