Submissions for variant NM_024312.5(GNPTAB):c.2693del (p.Lys898fs)

dbSNP: rs281864999

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000032323	SCV000699478	pathogenic	Pseudo-Hurler polydystrophy	2016-07-28	criteria provided, single submitter	clinical testing	Variant summary: The GNPTAB c.2693delA (p.Lys898Serfs) 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. The variant of interest was not found in controls (ExAC, 1000 Gs or ESP) and has been reported in one affected individual who was diagnosed with ML III and was compound heterozygous for the variant of interest and an exon 2 duplication. GeneReviews classifies the variant as "pathogenic." Therefore, taking all available lines of evidence into consideration the varinat of interest has been classified as Pathogenic.
Counsyl	RCV000673774	SCV000799017	likely pathogenic	Mucolipidosis type II; Pseudo-Hurler polydystrophy	2018-04-04	criteria provided, single submitter	clinical testing
Kariminejad - Najmabadi Pathology & Genetics Center	RCV001814018	SCV001755530	pathogenic	not provided	2021-07-10	criteria provided, single submitter	clinical testing
Invitae	RCV000673774	SCV002219883	pathogenic	Mucolipidosis type II; Pseudo-Hurler polydystrophy	2023-03-21	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 39058). This premature translational stop signal has been observed in individual(s) with mucolipidosis III (PMID: 19197337). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Lys898Serfs*13) 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).
GeneReviews	RCV000032323	SCV000055968	not provided	Pseudo-Hurler polydystrophy		no assertion provided	literature only
Department of Genetics and Endocrinology, Guangzhou Women and Children’s Medical Center	RCV003984809	SCV004041873	pathogenic	Mucolipidosis		no assertion criteria provided	clinical testing