ClinVar Miner

Submissions for variant NM_024312.5(GNPTAB):c.344_345del (p.Thr115fs)

dbSNP: rs281864954
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000726917 SCV000704145 pathogenic not provided 2016-12-02 criteria provided, single submitter clinical testing
Counsyl RCV000674596 SCV000799960 pathogenic Mucolipidosis type II; Pseudo-Hurler polydystrophy 2018-05-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000674596 SCV001410924 pathogenic Mucolipidosis type II; Pseudo-Hurler polydystrophy 2023-11-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr115Asnfs*5) 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 (rs761987059, gnomAD 0.03%). This premature translational stop signal has been observed in individuals with mucolipidosis (PMID: 19617216). ClinVar contains an entry for this variant (Variation ID: 39073). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001255581 SCV001432077 pathogenic Mucolipidosis 2020-08-07 criteria provided, single submitter clinical testing Variant summary: GNPTAB c.344_345delCA (p.Thr115AsnfsX5) 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 4.8e-05 in 251084 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in GNPTAB causing Mucolipidosis (4.8e-05 vs 0.0022), allowing no conclusion about variant significance. c.344_345delCA has been reported in the literature in multiple individuals in compound heterozygous and homozygous states affected with Mucolipidosis II (Cathey_2010, Kollmann_2013). 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. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
GeneDx RCV000726917 SCV005078143 likely pathogenic not provided 2023-06-12 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; This variant is associated with the following publications: (PMID: 24127423, 19617216, 30882951, 32182687, 25601403)
GeneReviews RCV000032339 SCV000055984 not provided Mucolipidosis type II no assertion provided literature only
Natera, Inc. RCV000032339 SCV002088609 pathogenic Mucolipidosis type II 2020-03-16 no assertion criteria provided clinical testing

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