ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3379_3380del (p.Met1127fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001064156 SCV001229038 pathogenic Niemann-Pick disease type C1 2019-03-25 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the NPC1 gene (p.Met1127Valfs*130). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 152 amino acids of the NPC1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NPC1-related conditions. This variant disrupts the C-terminus of the NPC1 protein. Other variant(s) that disrupt this region (p.Arg1173Lysfs*85, p.Phe1199Leufs*43) have been determined to be pathogenic (PMID: 10521290, 11479732, 12401890, 25425405, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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