Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000000251 | SCV000220824 | likely pathogenic | Aspartylglucosaminuria | 2014-10-21 | criteria provided, single submitter | literature only | |
Invitae | RCV000000251 | SCV003525619 | pathogenic | Aspartylglucosaminuria | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 8 of the AGA gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely disrupts the C-terminus of the protein. This variant is present in population databases (rs386833437, gnomAD 0.01%). Disruption of this splice site has been observed in individual(s) with aspartylglucosaminuria (PMID: 1722323, 1879549). ClinVar contains an entry for this variant (Variation ID: 227). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that disruption of this splice site affects AGA function (PMID: 1879549). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that disruption of this splice site results in skipping of exon 8 and introduces a new termination codon (PMID: 1879549). However the mRNA is not expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000000251 | SCV000020395 | pathogenic | Aspartylglucosaminuria | 1991-12-15 | no assertion criteria provided | literature only | |
Juha Muilu Group; Institute for Molecular Medicine Finland |
RCV000000251 | SCV000081797 | probable-pathogenic | Aspartylglucosaminuria | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. |