ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.790_793del (p.Phe264fs) (rs121913320)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414059 SCV000490836 pathogenic not provided 2016-06-29 criteria provided, single submitter clinical testing The c.790_793delTTTG variant in the STK11 gene has been reported previously in association with Peutz-Jegher syndrome (for examples, see Resta et al., 1998; Aretz et al., 2005; Wong et al., 2015). This variant has reportedly occurred de novo in at least one individual (Aretz et al., 2005). Functional studies show c.790_793delTTTG causes protein truncation and is associated with reduced or absent phosphorylation activity, protein mislocalization, and an inability to suppress cell growth (Boudeau et al., 2003). The deletion causes a frameshift starting with codon Phenylalanine 264, changes this amino acid to an Arginine residue and creates a premature Stop codon at position 22 of the new reading frame, denoted p.Phe264ArgfsX22. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Based on the currently available evidence, we consider c.790_793delTTTG to be pathogenic.
Ambry Genetics RCV000492099 SCV000580899 pathogenic Hereditary cancer-predisposing syndrome 2015-11-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000632833 SCV000754029 pathogenic Peutz-Jeghers syndrome 2017-10-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe264Argfs*22) in the STK11 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with Peutz-Jeghers syndrome, being described to be de novo in one of them (PMID: 9809980, 15863673, 16287113, 17010210, 23718779, 26979979). This variant is also known as c.787del4 in the literature. ClinVar contains an entry for this variant (Variation ID: 372523). Loss-of-function variants in STK11 are known to be pathogenic (PMID: 15188174, 16287113). For these reasons, this variant has been classified as Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000414059 SCV000884613 pathogenic not provided 2017-09-06 criteria provided, single submitter clinical testing

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