Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000437701 | SCV000531361 | uncertain significance | not provided | 2016-09-07 | criteria provided, single submitter | clinical testing | The L17F variant in the AGRN gene has not been reported previously as a pathogenic variant, nor asa benign variant, to our knowledge. The L17F variant was not observed in approximately 2700individuals of European and African American ancestry in the NHLBI Exome Sequencing Project,indicating it is not a common benign variant in these populations. This substitution occurs at aposition that is conserved in mammals. However, the L17F variant is a conservative amino acidsubstitution, which is not likely to impact secondary protein structure as these residues share similarproperties and in silico analysis predicts this variant likely does not alter the proteinstructure/function. We interpret L17F as a variant of uncertain significance. |
Invitae | RCV003114567 | SCV003786949 | uncertain significance | Congenital myasthenic syndrome 8 | 2022-03-26 | criteria provided, single submitter | clinical testing | 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. 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: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 388958). This variant has not been reported in the literature in individuals affected with AGRN-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.03%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 17 of the AGRN protein (p.Leu17Phe). |