Submissions for variant NM_000271.5(NPC1):c.721C>T (p.Gln241Ter) (rs1064795718)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000478255	SCV000571787	likely pathogenic	not provided	2016-10-25	criteria provided, single submitter	clinical testing	The Q241X variant in the NPC1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q241X variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret Q241X as a likely pathogenic variant.
Invitae	RCV000694249	SCV000822684	pathogenic	Niemann-Pick disease type C1	2018-05-18	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln241*) in the NPC1 gene. It is expected to result in an absent or disrupted protein product. 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 disease. ClinVar contains an entry for this variant (Variation ID: 422340). Loss-of-function variants in NPC1 are known to be pathogenic (PMID: 9211850). For these reasons, this variant has been classified as Pathogenic.