Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000114427 | SCV003284619 | likely pathogenic | Congenital myasthenic syndrome 8 | 2022-06-14 | criteria provided, single submitter | clinical testing | 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. Experimental studies have shown that this missense change affects AGRN function (PMID: 22205389, 30994901). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 126555). This missense change has been observed in individual(s) with congenital myasthenic syndrome (PMID: 22205389, 33756069). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1727 of the AGRN protein (p.Val1727Phe). |
OMIM | RCV000114427 | SCV000148369 | pathogenic | Congenital myasthenic syndrome 8 | 2012-07-01 | no assertion criteria provided | literature only | |
Gene |
RCV000235038 | SCV000292411 | not provided | Congenital myasthenic syndrome | no assertion provided | literature only |