ClinVar Miner

Submissions for variant NM_001079802.2(FKTN):c.607C>T (p.Arg203Ter) (rs746763506)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000490403 SCV000267316 pathogenic Fukuyama congenital muscular dystrophy; Limb-girdle muscular dystrophy-dystroglycanopathy, type C4; Congenital muscular dystrophy-dystroglycanopathy without mental retardation, type B4 2016-03-18 criteria provided, single submitter reference population
Invitae RCV000234557 SCV000285819 pathogenic Walker-Warburg congenital muscular dystrophy 2019-04-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg203*) in the FKTN gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs746763506, ExAC 0.009%). This variant has been observed in individuals affected with FKTN-related disease (PMID: 11165248, 20961758, 26809617). ClinVar contains an entry for this variant (Variation ID: 225359). 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.
GeneDx RCV000255310 SCV000322218 pathogenic not provided 2018-05-23 criteria provided, single submitter clinical testing The R203X variant in the FKTN gene has been reported as a homozygous variant in one patent with Fukuyama-type congenital muscular dystrophy (Kobayashi et al., 2001). The R203X variant is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the FKTN gene have been reported in Human Gene Mutation Database in association with FKTN-related disorders (Stenson et al., 2014). Furthermore, the R203X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). In summary, R203X in the FKTN gene is interpreted as a pathogenic variant.
Integrated Genetics/Laboratory Corporation of America RCV000590733 SCV000698717 pathogenic Fukuyama congenital muscular dystrophy 2016-05-06 criteria provided, single submitter clinical testing Variant summary: The FKTN variant, c.607C>T (p.Arg203X) causes a nonsense mutation in exon 5 resulting in a premature termination codon, a known mechanism for disease, as these types of variants are predicted to cause transcript degradation through nonsense mediated decay or produce a truncated protein. The varinat of interest was observed in the large, broad control population, ExAC, with an allele frequency of 1/121290, which does not exceed the estimated maximum expected allele frequency for a pathogenic FKTN variant of 1/200 for Fukuyama Congenital Muscular Dystrophy. The variant of interest has been reported in multiple affected individuals dx with Fukuyama Congenital Muscular Dystrophy (patient was homozygous for variant) and Muscular dystrophy-dystroglycanopathy(limb-girdle) via publications. One reputable database cites the variant as disease-causing. Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Pathogenic.
Counsyl RCV000590733 SCV000790450 pathogenic Fukuyama congenital muscular dystrophy 2017-03-21 criteria provided, single submitter clinical testing

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