Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001056811 | SCV001221275 | pathogenic | Niemann-Pick disease, type C1 | 2023-03-23 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects NPC1 function (PMID: 31699992). 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: 2964). This missense change has been observed in individuals with NPC1-related conditions (PMID: 10480349, 23711246, 26666848). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1088 of the NPC1 protein (p.Tyr1088Cys). |
OMIM | RCV000003098 | SCV000023256 | pathogenic | Niemann-Pick disease, type C1, juvenile form | 1999-07-01 | no assertion criteria provided | literature only |