Submissions for variant NM_000271.5(NPC1):c.3717C>T (p.His1239=)

gnomAD frequency: 0.00030  dbSNP: rs34624018

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000305924	SCV000333819	uncertain significance	not provided	2018-01-30	criteria provided, single submitter	clinical testing
Invitae	RCV000544982	SCV000650849	likely benign	Niemann-Pick disease, type C1	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000544982	SCV001282150	uncertain significance	Niemann-Pick disease, type C1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Pars Genome Lab	RCV000544982	SCV001736768	uncertain significance	Niemann-Pick disease, type C1	2021-05-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000305924	SCV001871116	likely benign	not provided	2021-02-08	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000305924	SCV002498356	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	NPC1: BP4, BP7
Ambry Genetics	RCV002347990	SCV002620635	likely benign	Inborn genetic diseases	2022-03-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003920049	SCV004729533	likely benign	NPC1-related disorder	2019-06-10	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Natera, Inc.	RCV000544982	SCV002095156	benign	Niemann-Pick disease, type C1	2019-10-22	no assertion criteria provided	clinical testing