Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000498134 | SCV000589561 | pathogenic | not provided | 2017-06-13 | criteria provided, single submitter | clinical testing | The R307X pathogenic variant in the FKTN gene has been reported as a homozygous change in an individual with Walker-Warburg syndrome (Godfrey et al., 2007). The R307X variant was also identified in an individual with Fukuyama-type congenital muscular dystrophy who also had the common Japanese founder mutation (Yoshioka et al., 2008). The R307X 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 pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. |
| Integrated Genetics/Laboratory Corporation of America | RCV000169165 | SCV000698720 | pathogenic | Fukuyama congenital muscular dystrophy | 2019-03-18 | criteria provided, single submitter | clinical testing | Variant summary: FKTN c.919C>T (p.Arg307X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as likely pathogenic/pathogenic by our laboratory (eg. c.1106delT (p.Phe369fsX37) and c.1167dupA (p.Phe390fsX14)). The variant allele was found at a frequency of 2e-05 in 244338 control chromosomes (gnomAD). c.919C>T has been reported in the literature in individuals affected with Walker-Warburg Syndrome, Fukuyama-type congenital muscular dystrophy, and unexplained limb-girdle muscle weakness (Godfrey_2007, Yoshioka_2008, Johnson_2018). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV000795218 | SCV000934664 | pathogenic | Walker-Warburg congenital muscular dystrophy | 2019-12-19 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg307*) in the FKTN gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs267606814, ExAC 0.002%). This variant has been observed as homozygous in an individual affected with Walker-Warburg syndrome (PMID: 17878207) and in combination with another FKTN variant in an individual affected with Fukuyama-type congenital muscular dystrophy (PMID: 17597323). ClinVar contains an entry for this variant (Variation ID: 3216). Loss-of-function variants in FKTN are known to be pathogenic (PMID: 17044012, 17878207, 18752264). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000169165 | SCV001163212 | pathogenic | Fukuyama congenital muscular dystrophy | criteria provided, single submitter | clinical testing | ||
| OMIM | RCV000003371 | SCV000023529 | pathogenic | Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A4 | 2007-10-01 | no assertion criteria provided | literature only | |
| Counsyl | RCV000169165 | SCV000220393 | pathogenic | Fukuyama congenital muscular dystrophy | 2016-08-19 | no assertion criteria provided | clinical testing |