ClinVar Miner

Submissions for variant NM_000157.4(GBA1):c.1495G>A (p.Val499Met)

gnomAD frequency: 0.00006  dbSNP: rs369068553
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000994116 SCV001147441 uncertain significance not provided 2023-06-01 criteria provided, single submitter clinical testing GBA1: PM2, PM5, PM3:Supporting
Fulgent Genetics, Fulgent Genetics RCV002481763 SCV002782478 uncertain significance Lewy body dementia; Gaucher disease type I; Gaucher disease type II; Gaucher disease type III; Gaucher disease perinatal lethal; Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome; Parkinson disease, late-onset 2021-08-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005236510 SCV005883542 uncertain significance not specified 2024-12-13 criteria provided, single submitter clinical testing Variant summary: GBA1 c.1495G>A (p.Val499Met) results in a conservative amino acid change located in the Glycosyl hydrolase family 30 beta sandwich domain (IPR033452) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.7e-05 in 1613138 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in GBA1 causing Gaucher Disease (2.7e-05 vs 0.005), allowing no conclusion about variant significance. c.1495G>A has been reported in the literature in the heterozygous state in individuals affected with Parkinsondisease and in the homozygous state in individuals from one familiy affected with Gaucher Disease who were also homozygous for other missense variants in GBA1 (Zhang_2018, Ren_2023, ZHao_2021, Marano_2024, Erdem_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Gaucher Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. This variant is also known as V460M. The following publications have been ascertained in the context of this evaluation (PMID: 30126557, 38843618, 34951095, 29527153, 34867278). ClinVar contains an entry for this variant (Variation ID: 806227). Based on the evidence outlined above, the variant was classified as uncertain significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.