Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000723447 | SCV000226963 | pathogenic | not provided | 2014-06-02 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000664622 | SCV000788618 | pathogenic | Mucolipidosis type II; Pseudo-Hurler polydystrophy | 2017-04-28 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000723447 | SCV000890263 | pathogenic | not provided | 2018-09-10 | criteria provided, single submitter | clinical testing | The R1189X nonsense variant in the GNPTAB gene has been reported previously in association with mucolipidosis II and III in several unrelated individuals who were homozygous for R1189X or heterozygous for R1189X and another variant in the GNPTAB gene (Paik et al., 2005; Otomo et al. 2009; Yang et al. 2017). The R1189X variant is a common pathogenic variant in several East Asian populations (Otomo et al. 2009). The R1189X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. |
Invitae | RCV000664622 | SCV001237189 | pathogenic | Mucolipidosis type II; Pseudo-Hurler polydystrophy | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg1189*) in the GNPTAB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GNPTAB are known to be pathogenic (PMID: 19617216, 25107912). This variant is present in population databases (rs137852897, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with mucolipidosis II (PMID: 16116615, 23926388). ClinVar contains an entry for this variant (Variation ID: 2764). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193438 | SCV001362264 | pathogenic | Mucolipidosis | 2020-08-03 | criteria provided, single submitter | clinical testing | Variant summary: GNPTAB c.3565C>T (p.Arg1189X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 2e-05 in 251436 control chromosomes. c.3565C>T has been reported in the literature in multiple individuals affected with Mucolipidosis (ML) in whom a diagnosis of ML was based on clinical manifestations and lysosomal enzyme activities in serum, lymphocyte and skin fibroblasts (example, Cathey_2010, Ma_2011, Otomo_2009). These data indicate that the variant is very likely to be associated with disease. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Daryl Scott Lab, |
RCV003398424 | SCV004102690 | pathogenic | GNPTAB-related disorder | 2023-11-10 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000002891 | SCV000023049 | pathogenic | Mucolipidosis type II | 2009-03-01 | no assertion criteria provided | literature only | |
OMIM | RCV000002892 | SCV000023050 | pathogenic | Pseudo-Hurler polydystrophy | 2009-03-01 | no assertion criteria provided | literature only | |
Gene |
RCV000002892 | SCV000054685 | pathologic | Pseudo-Hurler polydystrophy | 2012-05-10 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |
Gene |
RCV000002891 | SCV000055990 | not provided | Mucolipidosis type II | no assertion provided | literature only | ||
Natera, |
RCV000002891 | SCV001457937 | pathogenic | Mucolipidosis type II | 2020-09-16 | no assertion criteria provided | clinical testing |