Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000596349 | SCV000704660 | uncertain significance | not provided | 2016-12-15 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000649025 | SCV000770846 | pathogenic | Niemann-Pick disease, type C1 | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 842 of the NPC1 protein (p.Phe842Leu). This variant is present in population databases (rs190298665, gnomAD 0.02%). This missense change has been observed in individuals with Niemann-Pick Disease Type C (PMID: 29453517; Invitae). ClinVar contains an entry for this variant (Variation ID: 499258). 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%. This variant disrupts the p.Phe842 amino acid residue in NPC1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). 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. |
New York Genome Center | RCV000649025 | SCV002099149 | uncertain significance | Niemann-Pick disease, type C1 | 2021-04-02 | criteria provided, single submitter | clinical testing | The c.2524T>C, p.Phe842Leu missense variant identified in NPC1 has been reported in trans with a pathogenic variant in a 31-year-old patient with Niemann-Pick disease type C [PMID: 29453517]. This variant has twenty nine heterozygous alleles in the gnomAD v3 database consistent with the carrier frequency and in silico tools predict a deleterious effect. Based on the available evidence, the variant c.2524T>C, p.Phe842Leu in the NPC1gene is classified as a variant of uncertain significance. |
Revvity Omics, |
RCV000649025 | SCV003816041 | uncertain significance | Niemann-Pick disease, type C1 | 2020-03-12 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003952965 | SCV004767838 | likely pathogenic | NPC1-related condition | 2023-12-20 | criteria provided, single submitter | clinical testing | The NPC1 c.2524T>C variant is predicted to result in the amino acid substitution p.Phe842Leu. This variant has been reported in the compound heterozygous state in an individual with adult-onset Niemann-Pick disease type C (Zeiger et al. 2018. PubMed ID: 29453517) and was also identified in the analysis of a large sequencing dataset that did not include individuals with Niemann-Pick disease (Wassif et al. 2015. PubMed ID: 25764212). Additionally, this variant was seen in the compound heterozygous state in a patient at PreventionGenetics with biochemical findings that confirmed the diagnosis of Niemann-Pick disease. In summary, we interpret this variant as likely pathogenic. |
Natera, |
RCV000649025 | SCV001455861 | uncertain significance | Niemann-Pick disease, type C1 | 2020-09-16 | no assertion criteria provided | clinical testing |