Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000158970 | SCV000220410 | likely pathogenic | Niemann-Pick disease, type C1 | 2014-06-14 | criteria provided, single submitter | literature only | |
Fulgent Genetics, |
RCV000158970 | SCV000611220 | pathogenic | Niemann-Pick disease, type C1 | 2021-10-22 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000158970 | SCV000650835 | pathogenic | Niemann-Pick disease, type C1 | 2023-12-25 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 543 of the NPC1 protein (p.Pro543Leu). This variant is present in population databases (rs369368181, gnomAD 0.01%). This missense change has been observed in individuals with Niemann-Pick Type C disease (PMID: 12955717, 16126423, 19744920, 22476655, 22676771). ClinVar contains an entry for this variant (Variation ID: 181455). 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. |
Laboratory for Molecular Medicine, |
RCV000610038 | SCV000731399 | pathogenic | Niemann-Pick disease, type C | 2017-02-14 | criteria provided, single submitter | clinical testing | The p.Pro543Leu (NM_000271.4 c.1628C>T) variant in NPC1 has been reported in 1 h omozygous and 4 compound heterozygous individuals with Niemann-Pick disease type C (Millat 2005, Garver 2010, Heron 2012, and Chien 2013). This variant is absen t from ExAC but has been identified in 1/8,600 of European chromosomes by the NH LBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs3693681 81). In summary, this variant meets criteria to be classified as pathogenic for Niemann-Pick disease type C in an autosomal recessive manner based upon its bial lelic occurrence in patients and low frequency in controls. |