ClinVar Miner

Submissions for variant NM_024312.5(GNPTAB):c.3091C>T (p.Arg1031Ter)

gnomAD frequency: 0.00001  dbSNP: rs281865009
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667295 SCV000791725 pathogenic Mucolipidosis type II; Pseudo-Hurler polydystrophy 2017-05-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780316 SCV000917483 pathogenic Mucolipidosis 2017-09-08 criteria provided, single submitter clinical testing Variant summary: The GNPTAB c.3091C>T (p.Arg1031X) variant results in a premature termination codon, predicted to cause a truncated or absent GNPTAB 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.3410T>A (p.Leu1137X) and c.3503_3504delTC (p.Leu1168fsX5)). This variant was found in 1/246136 control chromosomes at a frequency of 0.0000041, which does not exceed the estimated maximal expected allele frequency of a pathogenic GNPTAB variant (0.0022361). Multiple publications have cited the variant in compound heterozygote ML2 individuals. A reputable database, GeneReviews, classifies the variant as "pathogenic." Taken together, this variant is classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000667295 SCV001372673 pathogenic Mucolipidosis type II; Pseudo-Hurler polydystrophy 2023-11-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1031*) 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 (rs281865009, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with mucolipidosis II (PMID: 19617216, 23227064, 29872134). ClinVar contains an entry for this variant (Variation ID: 39065). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
MGZ Medical Genetics Center RCV002288528 SCV002581837 pathogenic Pseudo-Hurler polydystrophy 2021-09-02 criteria provided, single submitter clinical testing
GeneReviews RCV000032330 SCV000055975 not provided Mucolipidosis type II no assertion provided literature only
Natera, Inc. RCV000032330 SCV001457941 pathogenic Mucolipidosis type II 2020-09-16 no assertion criteria provided clinical testing

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