Submissions for variant NM_000271.5(NPC1):c.2713C>T (p.Gln905Ter) (rs917070773)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV000474466	SCV000538195	likely pathogenic	Niemann-Pick disease type C1	2016-09-16	criteria provided, single submitter	clinical testing	The c.2713 C>T (p.Gln905Ter) in the NPC1 gene is a novel stop-gain variant that is predicted to result in premature truncation of the NPC1 protein. This variant was not found in the 1000 Genomes, Exome Variant Server (EVS) or ExAC databases. Thus, it is presumed to be rare. The Gln905 amino acid residue is highly conserved and insilico algorithms predict the variant to be pathogenic. Based on the combined evidence, this variant is classified as likely pathogenic for Niemann-Pick disease, type C1.
Invitae	RCV000474466	SCV000650841	pathogenic	Niemann-Pick disease type C1	2018-09-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal at codon 905 (p.Gln905*) of the NPC1 gene. It is expected to result in an absent or disrupted protein product. While this variant has not been reported in the literature, loss-of-function variants in NPC1 are known to be pathogenic (PMID: 19252935, 23433426). For these reasons, this variant has been classified as Pathogenic.