ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.2002A>T (p.Lys668Ter)

gnomAD frequency: 0.00001  dbSNP: rs758168173
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665507 SCV000789645 uncertain significance GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2017-02-08 criteria provided, single submitter clinical testing
GeneDx RCV001771920 SCV001993086 uncertain significance not provided 2019-02-28 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation, although loss-of-function variants have not been reported downstream of this position in the protein; The K668X variant is observed in 6/18,868 (0.0318%) alleles from individuals of East Asian background in large population cohorts (Lek et al., 2016).; This variant is associated with the following publications: (PMID: 30833958)
Invitae RCV001868203 SCV002248400 uncertain significance Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2022-07-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys668*) in the GLB1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 10 amino acid(s) of the GLB1 protein. This variant is present in population databases (rs758168173, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with GLB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 550693). This variant disrupts a region of the GLB1 protein in which other variant(s) (p.Val677Gly) have been observed in individuals with GLB1-related conditions (PMID: 33558080). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV000665507 SCV002781271 uncertain significance GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2022-04-28 criteria provided, single submitter clinical testing

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