ClinVar Miner

Submissions for variant NM_024312.5(GNPTAB):c.1090C>T (p.Arg364Ter) (rs200646278)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669478 SCV000794235 pathogenic I cell disease; Pseudo-Hurler polydystrophy 2017-09-20 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000669478 SCV000893263 pathogenic I cell disease; Pseudo-Hurler polydystrophy 2018-10-31 criteria provided, single submitter clinical testing
GeneReviews RCV000032286 SCV000055929 pathologic I cell disease 2012-05-10 no assertion criteria provided curation Converted during submission to Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000780317 SCV000917484 pathogenic Mucolipidosis 2018-02-15 criteria provided, single submitter clinical testing Variant summary: GNPTAB c.1090C>T (p.Arg364X) 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 (e.g., c.1123C>T (p.Arg375X), c.1581delC (p.Cys528fsX19), c.2693delA (p.Lys898fsX13)). The variant allele was found at a frequency of 1.2e-05 in 246412 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in GNPTAB causing Mucolipidosis (1.2e-05 vs 0.0022), allowing no conclusion about variant significance. The c.1090C>T variant has been reported in the literature in multiple individuals affected with Mucolipidosis, both as a homozygous and compound heterozygous allele. These data indicate that the variant is very likely to be associated with disease. GeneReviews, a well established database, along with a clinical diagnostic laboratory classify the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000669478 SCV000958952 pathogenic I cell disease; Pseudo-Hurler polydystrophy 2018-10-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg364*) in the GNPTAB gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous or in combination with another GNPTAB variant in individuals affected with mucolipidosis II (PMID: 19617216, 23773965, 27662472). ClinVar contains an entry for this variant (Variation ID: 39021). Loss-of-function variants in GNPTAB are known to be pathogenic (PMID: 19617216, 25107912). For these reasons, this variant has been classified as Pathogenic.

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