ClinVar Miner

Submissions for variant NM_001079802.2(FKTN):c.1176C>A (p.Tyr392Ter)

dbSNP: rs1203741361
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001245464 SCV001418755 likely pathogenic Walker-Warburg congenital muscular dystrophy 2023-12-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr392*) in the FKTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 70 amino acid(s) of the FKTN protein. This variant is present in population databases (no rsID available, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with Walker-Warburg syndrome (PMID: 18752264, 22522420). ClinVar contains an entry for this variant (Variation ID: 969988). This variant disrupts a region of the FKTN protein in which other variant(s) (p.Asn442Ser) have been observed in individuals with FKTN-related conditions (PMID: 28785732). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Revvity Omics, Revvity RCV001780185 SCV002017783 likely pathogenic not provided 2019-07-08 criteria provided, single submitter clinical testing
AiLife Diagnostics, AiLife Diagnostics RCV001780185 SCV002501053 likely pathogenic not provided 2021-05-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV002327598 SCV002637133 likely pathogenic Cardiovascular phenotype 2022-07-28 criteria provided, single submitter clinical testing The p.Y392* variant (also known as c.1176C>A), located in coding exon 9 of the FKTN gene, results from a C to A substitution at nucleotide position 1176. This changes the amino acid from a tyrosine to a stop codon within coding exon 9. This alteration occurs at the 3' terminus of theFKTN gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 14.9% of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This alteration has been reported in an individual with Walker-Warburg syndrome, who was identified to have an additional alteration in FKTN (Manzini MC et al. Hum Mutat, 2008 Nov;29:E231-41). 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 RCV003469473 SCV004199718 pathogenic Dilated cardiomyopathy 1X 2023-10-14 criteria provided, single submitter clinical testing

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