ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.2234C>A (p.Ala745Glu) (rs752386083)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672740 SCV000797876 uncertain significance Niemann-Pick disease type C1 2018-02-13 criteria provided, single submitter clinical testing
Invitae RCV000672740 SCV000931568 uncertain significance Niemann-Pick disease type C1 2018-07-13 criteria provided, single submitter clinical testing This sequence change replaces alanine with glutamic acid at codon 745 of the NPC1 protein (p.Ala745Glu). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and glutamic acid. This variant is present in population databases (rs752386083, ExAC 0.002%). This variant has been observed in an individual affected with Niemann-Pick type C but no second allele was reported (PMID: 12955717). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; 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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