Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000000948 | SCV000919478 | pathogenic | Mucopolysaccharidosis type 7 | 2018-03-29 | criteria provided, single submitter | clinical testing | Variant summary: GUSB c.1521G>A (p.Trp507X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.1e-05 in 270504 control chromosomes. This frequency is not higher than expected for a pathogenic variant in GUSB causing Mucopolysaccharidosis Type VI (Sly Syndrome) (1.1e-05 vs 0.0011), allowing no conclusion about variant significance. c.1521G>A has been reported in the literature in two individuals affected with severe Mucopolysaccharidosis Type VI (Sly Syndrome) (Vervoort 1996, Yamada 1995). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence showing that B-glucuronidase enzyme activity of the variant allele was less than 10% of a normal control (Yamada 1995). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV000000948 | SCV001522960 | pathogenic | Mucopolysaccharidosis type 7 | 2019-06-30 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Invitae | RCV000000948 | SCV003295017 | pathogenic | Mucopolysaccharidosis type 7 | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp507*) in the GUSB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GUSB are known to be pathogenic (PMID: 19224584). This variant is present in population databases (rs121918179, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with mucopolysaccharidosis VII (PMID: 7633414). This variant is also known as W507X. ClinVar contains an entry for this variant (Variation ID: 900). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000000948 | SCV000021098 | pathogenic | Mucopolysaccharidosis type 7 | 1995-04-01 | no assertion criteria provided | literature only |