ClinVar Miner

Submissions for variant NM_001079802.2(FKTN):c.456_457del (p.Ser154fs)

dbSNP: rs760731888
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000479641 SCV000335826 pathogenic not provided 2015-10-08 criteria provided, single submitter clinical testing
GeneDx RCV000479641 SCV000572858 pathogenic not provided 2017-01-30 criteria provided, single submitter clinical testing The c.456_457delAC pathogenic variant in the FKTN gene has not previously been reported to our knowledge. This variant causes a shift in reading frame starting at codon Serine 154, changing it to a Tryptophan, and creating a premature stop codon at position 3 of the new reading frame, denoted p.Ser154TrpfsX3. This pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other downstream frameshift variants in the FKTN gene have been reported in Human Gene Mutation Database in association with FKTN-associated disorders (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. Furthermore, the c.456_457delAC variant has not been observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Invitae RCV001383504 SCV001582655 pathogenic Walker-Warburg congenital muscular dystrophy 2022-07-15 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 283622). This variant has not been reported in the literature in individuals affected with FKTN-related conditions. This variant is present in population databases (rs760731888, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Ser154Trpfs*3) in the FKTN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FKTN are known to be pathogenic (PMID: 17044012, 17878207, 18752264).
Fulgent Genetics, Fulgent Genetics RCV002487209 SCV002784005 likely pathogenic Dilated cardiomyopathy 1X; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4; Autosomal recessive limb-girdle muscular dystrophy type 2M; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1; Muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4 2021-08-03 criteria provided, single submitter clinical testing

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