ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.48T>G (p.Leu16=)

gnomAD frequency: 0.00011  dbSNP: rs201449986
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 16
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000035304 SCV000058952 likely benign not specified 2013-02-08 criteria provided, single submitter clinical testing Leu16Leu in exon 1 of GLA: This variant is not expected to have clinical signifi cance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 1/6728 European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.ed/EVS/;). Leu16Leu in exon 1 of GLA (allele frequency = 1/6728) **
Illumina Laboratory Services, Illumina RCV000352576 SCV000481404 uncertain significance Hypertrophic cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000391328 SCV000481405 likely benign Fabry disease 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx RCV001703454 SCV000513152 likely benign not provided 2018-10-23 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 26866599)
Invitae RCV000391328 SCV000556165 likely benign Fabry disease 2024-01-25 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000391328 SCV000913690 likely benign Fabry disease 2018-05-29 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group, Broad Institute RCV000391328 SCV001423097 likely benign Fabry disease 2020-01-22 criteria provided, single submitter curation The c.48T>G variant in GLA has not been previously reported in individuals with Fabry disease, and has been identified in 0.039% (36/92630) of European (non-Finnish) chromosomes, including 5 hemizygotes, 0.019% (1/5335) of other chromosomes, and 0.011% (3/28053) of Latino chromosomes, including 1 hemizygote, by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs201449986). This variant has also been reported in ClinVar as likely bengin by the Laboratory for Molecular Medicine (Partners Healthcare), GeneDx, and Invitae and a VUS by Illumina Clinical Services Laboratory (ID:42455). Computational prediction tools, including splice predictors, and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely benign. ACMG/AMP Criteria applied: BS1, BP7 (Richards 2015).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000035304 SCV001478601 likely benign not specified 2021-01-21 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000391328 SCV002054828 likely benign Fabry disease 2021-07-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002326722 SCV002634597 likely benign Cardiovascular phenotype 2018-07-06 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Revvity Omics, Revvity Omics RCV001703454 SCV003816836 uncertain significance not provided 2021-01-21 criteria provided, single submitter clinical testing
Natera, Inc. RCV000391328 SCV001458764 likely benign Fabry disease 2020-09-16 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001703454 SCV001931661 likely benign not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001703454 SCV001952205 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001703454 SCV001964057 likely benign not provided no assertion criteria provided clinical testing
Cohesion Phenomics RCV000352576 SCV003803078 likely benign Hypertrophic cardiomyopathy 2022-09-29 no assertion criteria provided clinical testing

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.