ClinVar Miner

Submissions for variant NM_000027.4(AGA):c.677G>A (p.Gly226Asp) (rs386833431)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000300295 SCV000329847 pathogenic not provided 2016-09-30 criteria provided, single submitter clinical testing The G226D (c.667 G>A) pathogenic variant in the AGA gene has been reported previously in association with aspartylglucosaminuria (AGU) in two unrelated individuals who were apparently homozygous for G226D (Coulter-Mackie et al., 1999). Functional analysis of the c.667 G>A variant responsible for G226D found that it resulted the production of both normally spliced mRNA and transcripts with exon 6 skipping leading to a frameshift variant (Coulter-Mackie et al., 1999; Saarela et al., 2001). Additional functional analysis also found that the G226D substitution is associated with significantly reduced enzyme activity (Saarela et al., 2001; Saarela et al., 2004; Sui et al., 2014). Therefore, we interpret this variant to be a pathogenic variant.
Invitae RCV000049359 SCV001378538 likely pathogenic Aspartylglucosaminuria 2019-09-24 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 226 of the AGA protein (p.Gly226Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individuals affected with AGA-related conditions (PMID: 10399108). ClinVar contains an entry for this variant (Variation ID: 55950). This variant has been reported to affect AGA protein function (PMID: 18992224, 11309371). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049359 SCV000081791 probable-pathogenic Aspartylglucosaminuria no assertion criteria provided not provided Converted during submission to Likely pathogenic.
Counsyl RCV000049359 SCV001132325 likely pathogenic Aspartylglucosaminuria 2019-01-22 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.