ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3467A>T (p.Asn1156Ile)

dbSNP: rs28942105
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668091 SCV000792639 uncertain significance Niemann-Pick disease, type C1 2017-07-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000668091 SCV003442430 pathogenic Niemann-Pick disease, type C1 2022-09-12 criteria provided, single submitter clinical testing 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: 552768). This missense change has been observed in individual(s) with Niemann-Pick type C (PMID: 16098014). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1156 of the NPC1 protein (p.Asn1156Ile). This variant disrupts the p.Asn1156 amino acid residue in NPC1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9211849, 16098014, 17160617, 23430855). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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