Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588008 | SCV000696417 | likely pathogenic | Niemann-Pick disease, type C | 2017-08-03 | criteria provided, single submitter | clinical testing | Variant summary: The c.2670 (p.Tyr890*) variant in NPC1 gene is a nonsense change that results in the loss of the 389 amino acids of the protein (~30%). This change is predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. The variant is present in the large control population dataset of ExAC at a low frequency of 8.238e-06 (1/121384 chrs tested), which does not exceed the maximal expected frequency of a pathogenic allele (0.0027) in this gene. The variant has been identified in compound heterozygosity with known pathogenic allele in affected siblings presented with the classical biochemical phenotype NPC-1 characterized by massive lysosomal/ LE accumulation of unesterified cholesterol in cultured fibroblasts. Taken together, the variant was classified as Likely Pathogenic. |
Counsyl | RCV000665306 | SCV000789403 | likely pathogenic | Niemann-Pick disease, type C1 | 2017-02-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000665306 | SCV004297798 | pathogenic | Niemann-Pick disease, type C1 | 2023-11-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr890*) in the NPC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NPC1 are known to be pathogenic (PMID: 9211850). This variant is present in population databases (rs780592540, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Niemann-Pick Type C (PMID: 11349231). ClinVar contains an entry for this variant (Variation ID: 495788). For these reasons, this variant has been classified as Pathogenic. |