ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.2474A>G (p.Tyr825Cys)

gnomAD frequency: 0.00003  dbSNP: rs550562774
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410702 SCV000485432 likely pathogenic Niemann-Pick disease, type C1 2016-09-09 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000733999 SCV000862107 likely pathogenic not provided 2018-06-30 criteria provided, single submitter clinical testing
Invitae RCV000410702 SCV001586303 pathogenic Niemann-Pick disease, type C1 2024-01-21 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 825 of the NPC1 protein (p.Tyr825Cys). This variant is present in population databases (rs550562774, gnomAD 0.003%). This missense change has been observed in individual(s) with Niemann-Pick type C (PMID: 11349231, 16126423, 23433426, 27581084). ClinVar contains an entry for this variant (Variation ID: 370184). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
AiLife Diagnostics, AiLife Diagnostics RCV000733999 SCV002502652 likely pathogenic not provided 2022-03-24 criteria provided, single submitter clinical testing
Revvity Omics, Revvity Omics RCV000410702 SCV003815187 likely pathogenic Niemann-Pick disease, type C1 2022-09-28 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000733999 SCV001740521 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000733999 SCV001919623 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000733999 SCV001966719 likely pathogenic not provided no assertion criteria provided clinical testing

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