Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000666707 | SCV000791050 | pathogenic | Mucolipidosis type II; Pseudo-Hurler polydystrophy | 2017-04-25 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000666707 | SCV001219310 | pathogenic | Mucolipidosis type II; Pseudo-Hurler polydystrophy | 2023-12-26 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp467Ilefs*33) 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 (rs397507448, gnomAD 0.004%). This premature translational stop signal has been observed in individuals with mucolipidosis II and III alpha/beta (PMID: 19617216, 19634183, 28396763). ClinVar contains an entry for this variant (Variation ID: 39034). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193441 | SCV001362267 | pathogenic | Mucolipidosis | 2020-09-14 | criteria provided, single submitter | clinical testing | Variant summary: GNPTAB c.1399delG (p.Asp467IlefsX33) 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 251428 control chromosomes (gnomAD). The variant, c.1399delG, has been reported in the literature in compound heterozygosity and in homozygous form, in several individuals affected with Mucolipidosis (e.g. Tappino_2009, Cathey_2010, Wood_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Gene |
RCV003153314 | SCV003842681 | pathogenic | not provided | 2022-09-14 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 20301728, 25107912, 19617216, 19634183, 28396763, 24045841) |
Gene |
RCV000032299 | SCV000055943 | not provided | Mucolipidosis type II | no assertion provided | literature only | ||
Natera, |
RCV000032299 | SCV002088591 | pathogenic | Mucolipidosis type II | 2020-11-02 | no assertion criteria provided | clinical testing |