ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.395del (p.Pro132fs) (rs1057516462)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410028 SCV000485715 likely pathogenic Niemann-Pick disease type C1 2016-02-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001193401 SCV001362190 pathogenic Niemann-Pick disease, type C 2019-10-17 criteria provided, single submitter clinical testing Variant summary: NPC1 c.395delC (p.Pro132LeufsX10) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251404 control chromosomes (gnomAD). c.395delC has been reported in the literature in individuals affected with Niemann-Pick Disease Type C (e.g. Sun_2001, Park_2003, Paciorkowski_2008, Garver_2010, Lo_2010). These data indicate that the variant is likely to be associated with disease. Fibroblasts from individuals with this variant showed markedly reduced levels of intracellular cholesterol esterification (e.g. Sun_2001, Lo_2010). A ClinVar submission (evaluation after 2014) cite the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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