ClinVar Miner

Submissions for variant NM_024312.5(GNPTAB):c.1399del (p.Asp467fs)

dbSNP: rs397507448
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Total submissions: 6
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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 (formerly Invitae), Labcorp 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, LabCorp 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.
GeneDx 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)
GeneReviews RCV000032299 SCV000055943 not provided Mucolipidosis type II no assertion provided literature only
Natera, Inc. RCV000032299 SCV002088591 pathogenic Mucolipidosis type II 2020-11-02 no assertion criteria provided clinical testing

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