Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000492841 | SCV000583076 | uncertain significance | not provided | 2017-05-22 | criteria provided, single submitter | clinical testing | The P1997L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P1997L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, this substitution occurs at a position that is not conserved, and missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with congenital myasthenia syndrome (Stenson et al., 2014). |
Invitae | RCV000525192 | SCV000653984 | uncertain significance | Congenital myasthenic syndrome 8 | 2022-07-14 | 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 430302). This variant has not been reported in the literature in individuals affected with AGRN-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1997 of the AGRN protein (p.Pro1997Leu). |
Ambry Genetics | RCV002527106 | SCV003729428 | uncertain significance | Inborn genetic diseases | 2021-06-18 | criteria provided, single submitter | clinical testing | The c.5990C>T (p.P1997L) alteration is located in exon 36 (coding exon 36) of the AGRN gene. This alteration results from a C to T substitution at nucleotide position 5990, causing the proline (P) at amino acid position 1997 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |