Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV001579769 | SCV002771392 | pathogenic | not provided | 2022-01-24 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant results in the loss of the initiator methionine codon and is predicted to interfere with protein translation. This variant has been identified in multiple unrelated individuals with clinical features associated with this gene. In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. |
| Laboratory for Molecular Medicine, |
RCV004017228 | SCV004848638 | pathogenic | Friedreich ataxia 1 | 2022-04-12 | criteria provided, single submitter | clinical testing | The c.3G>T (p.Met1?) variant in FXN has been reported in five individuals with Friedreich ataxia who are compound heterozygous with a pathogenic GAA repeat expansion and segregated with disease in one affected individual from one family (Cossee 1997 PMID: 9090376, Zuhlke 1998 PMID: 9737785). It has also been identified 0.002% (1/41092) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant has also been reported in ClinVar as pathogenic (Variation ID 3983). This variant affects the translation initiation start codon (ATG) and is predicted to lead to a shortened protein that is <75% of the length of the full protein. Multiple additional variants with the same effect (p.Met1?) have been reported with pathogenic GAA repeat expansions in individuals with Friedreich ataxia (Cossee 1999 PMID: 9989622, Potter 2000 PMID: 10913738). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Friedreich ataxia. ACMG/AMP Criteria applied: PM3_VeryStrong, PM1, PVS1_Moderate, PM2_Supporting, PP1. |
| OMIM | RCV000004190 | SCV000024356 | pathogenic | Friedreich ataxia | 1998-07-01 | no assertion criteria provided | literature only | |
| Genome Diagnostics Laboratory, |
RCV001579769 | SCV001808456 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
| Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001579769 | SCV001951221 | pathogenic | not provided | no assertion criteria provided | clinical testing |