ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3263A>G (p.Tyr1088Cys) (rs28942106)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001056811 SCV001221275 uncertain significance Niemann-Pick disease type C1 2019-04-08 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 1088 of the NPC1 protein (p.Tyr1088Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with NPC1-related conditions (PMID: 10480349, 26666848). ClinVar contains an entry for this variant (Variation ID: 2964). 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.
OMIM RCV000003098 SCV000023256 pathogenic Niemann-Pick disease, type C1, juvenile form 1999-07-01 no assertion criteria provided literature only

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