ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3566A>G (p.Glu1189Gly)

gnomAD frequency: 0.00001  dbSNP: rs369098773
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000412462 SCV000486498 likely pathogenic Niemann-Pick disease, type C1 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000412462 SCV003443333 pathogenic Niemann-Pick disease, type C1 2023-11-07 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1189 of the NPC1 protein (p.Glu1189Gly). This variant is present in population databases (rs369098773, gnomAD 0.004%). This missense change has been observed in individual(s) with Niemann-Pick Type C (PMID: 11349231, 12205649, 26666848). ClinVar contains an entry for this variant (Variation ID: 371037). 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.
Genomics England Pilot Project, Genomics England RCV000412462 SCV001760423 pathogenic Niemann-Pick disease, type C1 no assertion criteria provided clinical testing

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