Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000484688 | SCV000566814 | pathogenic | not provided | 2017-02-21 | criteria provided, single submitter | clinical testing | The c.1887_1891delAAAAG variant was identified after homozygosity mapping in an individual with autosomal recessive Charcot Marie tooth disease (ARCMT); however no additional information was provided (Zimon et al., 2015). The c.1887_1891delAAAAG 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). The c.1887_1891delAAAAG variant in the FGD4 gene causes a frameshift starting with codon Lysine 630, changes this amino acid to a Asparagine residue and creates a premature Stop codon at position 5 of the new reading frame, denoted p.K630NfsX5. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, the c.1887_1891delAAAAG variant is considered to be a pathogenic variant. |
| Labcorp Genetics |
RCV001047299 | SCV001211247 | pathogenic | Charcot-Marie-Tooth disease type 4 | 2024-08-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys630Asnfs*5) in the FGD4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FGD4 are known to be pathogenic (PMID: 17564972). 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 premature translational stop signal has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 25231362). ClinVar contains an entry for this variant (Variation ID: 419181). For these reasons, this variant has been classified as Pathogenic. |
| Genomic Medicine Center of Excellence, |
RCV003447139 | SCV005438380 | pathogenic | Charcot-Marie-Tooth disease type 4H | 2024-12-18 | criteria provided, single submitter | clinical testing | |
| Inherited Neuropathy Consortium | RCV000789112 | SCV000928463 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only | ||
| Inherited Neuropathy Consortium Ii, |
RCV003447139 | SCV004174411 | uncertain significance | Charcot-Marie-Tooth disease type 4H | 2016-01-06 | no assertion criteria provided | literature only |