Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000778136 | SCV000914265 | uncertain significance | GNPTAB-Related Disorders | 2019-04-05 | criteria provided, single submitter | clinical testing | The GNPTAB c.775C>T (p.Gln259Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is not found in the 1000 Genomes Project, the Exome Sequencing Project, Exome Aggregation Consortium, or the Genome Aggregation Database in a region of good sequence coverage so the variant is presumed to be rare. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for GNPTAB-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Invitae | RCV003768421 | SCV004574090 | pathogenic | Mucolipidosis type II; Pseudo-Hurler polydystrophy | 2023-09-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln259*) 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 not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GNPTAB-related conditions. ClinVar contains an entry for this variant (Variation ID: 631534). For these reasons, this variant has been classified as Pathogenic. |