ClinVar Miner

Submissions for variant NM_006731.2(FKTN):c.919C>T (p.Arg307Ter) (rs267606814)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169165 SCV000220393 likely pathogenic Fukuyama congenital muscular dystrophy 2014-06-08 criteria provided, single submitter literature only
GeneDx 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 likely pathogenic Fukuyama congenital muscular dystrophy 2017-05-26 criteria provided, single submitter clinical testing Variant summary: The FKTN c.919C>T (p.Arg307X) variant results in a premature termination codon, predicted to cause a truncated or absent FKTN protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.1167dupA, p.Phe390fsX14). One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/103230 control chromosomes at a frequency of 0.0000097, which does not exceed the estimated maximal expected allele frequency of a pathogenic FKTN variant (0.0004564). The variant has been reported in the literature in a patient with WWS and FCMD. In addition, one clinical diagnostic laboratories classified this variant as likely pathogenic. Taken together, this variant is classified as likely pathogenic.
Invitae RCV000795218 SCV000934664 pathogenic Walker-Warburg congenital muscular dystrophy 2018-08-17 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.
OMIM RCV000003371 SCV000023529 pathogenic Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A4 2007-10-01 no assertion criteria provided literature only

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