Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Pediatric Genomic Medicine, |
RCV000514847 | SCV000610220 | uncertain significance | not provided | 2017-09-05 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002524985 | SCV003253750 | uncertain significance | Hereditary spastic paraplegia 75 | 2022-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 425 of the MAG protein (p.Arg425Gln). This variant is present in population databases (rs144213585, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MAG-related conditions. ClinVar contains an entry for this variant (Variation ID: 445646). 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"). 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 | RCV002524984 | SCV003702825 | uncertain significance | Inborn genetic diseases | 2021-04-15 | criteria provided, single submitter | clinical testing | The c.1274G>A (p.R425Q) alteration is located in exon 8 (coding exon 6) of the MAG gene. This alteration results from a G to A substitution at nucleotide position 1274, causing the arginine (R) at amino acid position 425 to be replaced by a glutamine (Q). Based on data from the Genome Aggregation Database (gnomAD) database, the MAG c.1274G>A alteration was observed in 0.01% (19/280178) of total alleles studied, with a frequency of 0.01% (18/127022) in the European (non-Finnish) subpopulation. This amino acid position is highly conserved in available vertebrate species. The p.R425Q alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |