ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3597del (p.Phe1199fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001056812 SCV001221276 likely pathogenic Niemann-Pick disease type C1 2019-04-08 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the NPC1 gene (p.Phe1199Leufs*43). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 80 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. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant disrupts the C-terminus of the NPC1 protein. Other variant(s) that disrupt this region (p.Leu1248Valfs*3, p.Phe1221Serfs*21, p.Pro1245Argfs*12, p.Pro1245Cysfs*12) have been observed in individuals with NPC1-related conditions (PMID: 10521290, 11479732, 12401890, 25425405). This suggests that this may be a clinically significant region of the protein. 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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