ClinVar Miner

Submissions for variant NM_198576.4(AGRN):c.2105C>T (p.Pro702Leu)

dbSNP: rs149814455
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000698736 SCV000827418 uncertain significance Congenital myasthenic syndrome 8 2022-10-24 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 702 of the AGRN protein (p.Pro702Leu). This variant is present in population databases (rs149814455, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with AGRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 576273). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences RCV003424292 SCV004116550 uncertain significance AGRN-related condition 2023-02-17 criteria provided, single submitter clinical testing The AGRN c.2105C>T variant is predicted to result in the amino acid substitution p.Pro702Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.099% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-979594-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
GenomeConnect - Brain Gene Registry RCV000698736 SCV004012808 not provided Congenital myasthenic syndrome 8 no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 06-14-2021 by Lab The Children's Hospital of Philadelphia. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.

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