ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.2833G>A (p.Asp945Asn) (rs1428599096)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000649023 SCV000770844 uncertain significance Niemann-Pick disease type C1 2017-12-21 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 945 of the NPC1 protein (p.Asp945Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been reported as heterozygous in individuals affected with Niemann-Pick disease type C for which no second variant in NPC1 was found (PMID: 12955717, 19744920). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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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