ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3259T>C (p.Phe1087Leu) (rs746715353)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670900 SCV000795813 likely pathogenic Niemann-Pick disease type C1 2017-11-17 criteria provided, single submitter clinical testing
Invitae RCV000670900 SCV000826899 likely pathogenic Niemann-Pick disease type C1 2019-07-30 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 1087 of the NPC1 protein (p.Phe1087Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with Niemann-Pick type C disease (PMID: 25349751, 26666848). An experimental study has shown that altering the equivalent phenylalanine residue in the yeast homolog of the protein results in protein destabilization and absent activity (PMID: 16138904). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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