Submissions for variant NM_000271.5(NPC1):c.2086del (p.Ala696fs)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centogene AG - the Rare Disease Company	RCV002284070	SCV002573477	pathogenic	Niemann-Pick disease, type C1	2022-08-30	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV002284070	SCV002604791	likely pathogenic	Niemann-Pick disease, type C1	2021-12-16	criteria provided, single submitter	clinical testing	NM_000271.4(NPC1):c.2086delG(A696Lfs*33) is expected to be pathogenic in the context of Niemann-Pick disease type C1. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in NPC1, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002284070	SCV004457545	pathogenic	Niemann-Pick disease, type C1	2023-04-22	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1705760). This variant has not been reported in the literature in individuals affected with NPC1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala696Leufs*33) in the NPC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NPC1 are known to be pathogenic (PMID: 9211850).