Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230935 | SCV003929090 | pathogenic | Gaucher disease | 2025-02-10 | criteria provided, single submitter | clinical testing | Variant summary: GBA1 c.260G>A (p.Arg87Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251272 control chromosomes. c.260G>A has been reported in the literature as a compound heterozygous genotype in individuals affected with Gaucher Disease (example, Erdos_2007, Biegstraaten_2013, Siebert_2013, Kang_2018, Huang_2020, Dimitriou_2020). These data indicate that the variant is likely to be associated with disease. A different variant affecting the same codon has been classified as pathogenic by our lab (c.259C>T, p.Arg87Trp), supporting the critical relevance of codon 87 to GBA1 protein function. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 22350617, 32547927, 17395504, 32165122, 29685539, 16293621, 23430543). ClinVar contains an entry for this variant (Variation ID: 2503944). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Foundation for Research in Genetics and Endocrinology, |
RCV003988098 | SCV004801944 | pathogenic | Gaucher disease type I | 2024-03-22 | criteria provided, single submitter | clinical testing | A homozygous missense variant in exon 3 of the GBA1 gene that results in the amino acid substitution of Glutamine for Arginine at codon 87 was detected. The observed variant c.260G>A (p.Arg87Gln) has not been reported in the 1000 genomes and gnomAD databases. The in-silico prediction of the variant is damaging by MutationTaster2 and DANN. In summary, the variant meets our criteria to be classified as pathogenic |