ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.1343A>T (p.Asp448Val) (rs757926581)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000675170 SCV000800791 likely pathogenic GM1 gangliosidosis type 2; Gangliosidosis GM1 type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2017-09-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000408320 SCV000443174 uncertain significance Morquio syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000292413 SCV000443175 likely pathogenic GM1 gangliosidosis 2017-04-27 criteria provided, single submitter clinical testing The GLB1 c.1343A>T (p.Asp448Val) missense variant has been reported in three studies in which it was found in a total of three individuals with GM1 gangliosidosis, including one in a homozygous state and two in a compound heterozygous state (Hofer et al. 2010; Higaki et al. 2011; Lei et al. 2012). The p.Asp448Val variant was absent from 50 controls and is reported at a frequency of 0.00023 in the East Asian population of the Exome Aggregation Consortium but this is based on two alleles in a region of good sequence coverage so the variant is presumed to be rare. Functional studies demonstrated that expression of the p.Asp448Val variant in COS-1 cells resulted in no detectable beta-galactosidase activity compared to wild type GLB1 (Hofer et al. 2010). Based on the evidence, the p.Asp448Val variant is classified as likely pathogenic for GM1 gangliosidosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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