Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Clinical Services Laboratory, |
RCV000330403 | SCV000459626 | likely pathogenic | FIG4-Related Disorders | 2016-06-14 | criteria provided, single submitter | clinical testing | The c.1666dup (p.Thr556AsnfsTer20) results in a frameshift, and is predicted to result in premature termination of the protein. The p.Thr556AsnfsTer20 variant has been reported in one study in two patients with Charcot-Marie-Tooth disease in a compound heterozygous state with a missense variant (Nicholson et al. 2011). No publications were found for this variant in relation to autosomal dominant amyotrophic lateral sclerosis. The p.Thr556AsnfsTer20 variant was absent from 206 controls and is not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium. Due to the potential impact of frameshift variants, the p.Thr556AsnfsTer20 variant is classified as likely pathogenic for FIG4-related disorders. |
| Invitae | RCV000798693 | SCV000938320 | pathogenic | Charcot-Marie-Tooth disease type 4 | 2018-10-19 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr556Asnfs*21) in the FIG4 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individuals affected with autosomal recessive Charcot-Marie-Tooth disease (PMID: 21705420). ClinVar contains an entry for this variant (Variation ID: 355040). Loss-of-function variants in FIG4 are known to be pathogenic (PMID: 23623387). For these reasons, this variant has been classified as Pathogenic. |