ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.743G>T (p.Gly248Val)

gnomAD frequency: 0.00001  dbSNP: rs1230538609
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota RCV001289552 SCV001477504 likely pathogenic Niemann-Pick disease, type C1 2020-10-08 criteria provided, single submitter clinical testing
Invitae RCV001289552 SCV003442633 uncertain significance Niemann-Pick disease, type C1 2022-07-08 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 248 of the NPC1 protein (p.Gly248Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with Niemann-Pick disease type C (PMID: 11349231). ClinVar contains an entry for this variant (Variation ID: 995578). 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: "Tolerated"; PolyPhen-2: "Possibly 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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