Submissions for variant NM_000271.5(NPC1):c.3451G>A (p.Ala1151Thr)

gnomAD frequency: 0.00002  dbSNP: rs765729815

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000689227	SCV000816868	pathogenic	Niemann-Pick disease, type C1	2023-09-27	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NPC1 protein function. ClinVar contains an entry for this variant (Variation ID: 568770). This missense change has been observed in individual(s) with Niemann-Pick disease type C1 (PMID: 19744920, 20718790, 27581084; Invitae). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1151 of the NPC1 protein (p.Ala1151Thr).
Eurofins Ntd Llc (ga)	RCV000734932	SCV000863112	likely pathogenic	not provided	2018-08-30	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000734932	SCV001740709	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000734932	SCV001972122	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000689227	SCV002095163	likely pathogenic	Niemann-Pick disease, type C1	2020-10-27	no assertion criteria provided	clinical testing