Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001038413 | SCV001201880 | uncertain significance | Congenital myasthenic syndrome 8 | 2022-03-18 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1154 of the AGRN protein (p.Met1154Val). This variant is present in population databases (rs371617418, gnomAD 0.007%). 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: 837139). 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Ambry Genetics | RCV002553043 | SCV003576767 | uncertain significance | Inborn genetic diseases | 2021-09-28 | criteria provided, single submitter | clinical testing | The c.3460A>G (p.M1154V) alteration is located in exon 20 (coding exon 20) of the AGRN gene. This alteration results from a A to G substitution at nucleotide position 3460, causing the methionine (M) at amino acid position 1154 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |