ClinVar Miner

Submissions for variant NM_001079802.2(FKTN):c.1129_1130del (p.Met377fs)

gnomAD frequency: 0.00001  dbSNP: rs1554761402
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000674108 SCV000799384 likely pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 2018-04-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV002325341 SCV002608188 likely pathogenic Cardiovascular phenotype 2022-09-28 criteria provided, single submitter clinical testing The c.1129_1130delAT variant, located in coding exon 8 of the FKTN gene, results from a deletion of two nucleotides at nucleotide positions 1129 to 1130, causing a translational frameshift with a predicted alternate stop codon (p.M377Vfs*26). This alteration occurs at the 3' terminus of theFKTN gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 18% of the protein. However, premature stop codons are typically deleterious in nature and a significant portion of the protein is affected (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Baylor Genetics RCV003472165 SCV004199736 likely pathogenic Dilated cardiomyopathy 1X 2023-12-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003768009 SCV004675911 pathogenic Walker-Warburg congenital muscular dystrophy 2023-11-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Met377Valfs*26) in the FKTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 85 amino acid(s) of the FKTN protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FKTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 557908). This variant disrupts a region of the FKTN protein in which other variant(s) (p.Asp455Metfs*12) have been determined to be pathogenic (PMID: 17044012). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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