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

dbSNP: rs1203741361

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000760536	SCV000890427	likely pathogenic	not provided	2023-10-05	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation, as the last 70 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV002536580	SCV002993548	likely pathogenic	Walker-Warburg congenital muscular dystrophy	2022-08-22	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 0.007%). This premature translational stop signal has been observed in individual(s) with Walker-Warburg syndrome (PMID: 22522420). ClinVar contains an entry for this variant (Variation ID: 620184). 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.
Baylor Genetics	RCV003465678	SCV004199716	likely pathogenic	Dilated cardiomyopathy 1X	2023-10-20	criteria provided, single submitter	clinical testing