Submissions for variant NM_000455.5(STK11):c.402_403del (p.Cys134fs)

dbSNP: rs587782424

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000161008	SCV000211719	pathogenic	Hereditary cancer-predisposing syndrome	2014-03-20	criteria provided, single submitter	clinical testing	The presence of the c.402_403delTG mutation was confirmed in the submitted specimen. The c.402_403delTG mutation in the STK11 gene causes a frameshift starting with codon Cysteine 134, changes this amino acid to a Tryptophan residue, and creates a premature Stop codon at position 28 of the new reading frame, denoted p.Cys134TrpfsX28. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense mediated mRNA decay. Although this mutation has not been previously reported to our knowledge. The variant is found in STK11 panel(s).
Invitae	RCV000703819	SCV000832740	pathogenic	Peutz-Jeghers syndrome	2023-02-27	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This sequence change creates a premature translational stop signal (p.Cys134Trpfs*28) in the STK11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in STK11 are known to be pathogenic (PMID: 15188174, 16287113). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Peutz-Jeghers syndrome (PMID: 20393878). ClinVar contains an entry for this variant (Variation ID: 182913). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV000703819	SCV002057362	pathogenic	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing