Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001052710 | SCV001216934 | pathogenic | Glycogen storage disease, type IV; Glycogen storage disease IV, classic hepatic | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 541 of the GBE1 protein (p.Asn541Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with glycogen storage disease (PMID: 25544507; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 848865). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271616 | SCV002555639 | likely pathogenic | Glycogen storage disease, type IV | 2023-08-17 | criteria provided, single submitter | clinical testing | Variant summary: GBE1 c.1621A>G (p.Asn541Asp) results in a conservative amino acid change located in the Glycosyl hydrolase, family 13, catalytic domain (IPR006047) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 152994 control chromosomes (gnomAD and publication data). c.1621A>G has been reported in the literature in compound heterozygous and homozygous individuals affected with Adult Polyglucosan Body Disease (examples: Sampaolo_2014, Carvalho_2021). In addition, GBE1 activity was below 25% of the normal rate in leukocytes and sural nerves in homozygous patients (Sampaolo_2014). These data indicate that the variant is likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 33517539, 30228975, 25544507). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV002271616 | SCV004198708 | likely pathogenic | Glycogen storage disease, type IV | 2024-03-05 | criteria provided, single submitter | clinical testing |