Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000412438 | SCV000486996 | likely pathogenic | Niemann-Pick disease, type C1 | 2016-09-22 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000412438 | SCV002227787 | pathogenic | Niemann-Pick disease, type C1 | 2023-07-14 | 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 1019 of the NPC1 protein (p.Tyr1019Cys). This variant is present in population databases (rs781261962, gnomAD 0.002%). This missense change has been observed in individual(s) with Niemann-Pick type C (PMID: 32138288). ClinVar contains an entry for this variant (Variation ID: 371419). 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. Studies have shown that this missense change alters NPC1 gene expression (PMID: 23430855). For these reasons, this variant has been classified as Pathogenic. |
Foundation for Research in Genetics and Endocrinology, |
RCV000412438 | SCV002574927 | pathogenic | Niemann-Pick disease, type C1 | 2022-04-12 | criteria provided, single submitter | clinical testing | A Homozygous missense variation in exon 21 of the NPC1 gene that results in the amino acid substitution of Cystine for Tyrosine at codon 1019 was detected. The observed variant c.3056A>G (p.Tyr1019Cys) has not been reported in the 1000 genomes and has a MAF of 000796% in the gnomAD database. The in silico prediction of the variant is damaging by PolyPhen-2 (HumDiv), LRT and MutationTaster2. In summary, the variant meets our criteria to be classified as pathogenic. |
Fulgent Genetics, |
RCV000412438 | SCV002778115 | likely pathogenic | Niemann-Pick disease, type C1 | 2022-02-15 | criteria provided, single submitter | clinical testing |