ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.1819C>T (p.Arg607Ter) (rs377130051)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255864 SCV000322457 pathogenic not provided 2015-12-17 criteria provided, single submitter clinical testing The R607X pathogenic variant in the NPC1 gene has been reported previously in association with Niemann-Pick Disease Type C, in an affected individual who was compound heterozygous for the R607X pathogenic variant and another variant (Bauer et al., 2002). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R607X variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret R607X as a pathogenic variant.
Integrated Genetics/Laboratory Corporation of America RCV000589541 SCV000696415 pathogenic Niemann-Pick disease, type C 2017-08-02 criteria provided, single submitter clinical testing Variant summary: The c.1819C>T (p.Arg607*) variant in NPC1 gene is a nonsense change that results in the loss of the 677 amino acids of the protein (~52%). This change is predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay and truncated protein that would be translated from this allele was not detected by western blot (Zampieri, 2013). The variant is absent from in the large control population dataset of ExAC (121384 chrs tested). The variant has been identified in compound heterozygosity with known pathogenic alleles in several affected individuals 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 Pathogenic.

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