Submissions for variant NM_000455.5(STK11):c.790_793del (p.Phe264fs)

dbSNP: rs121913320

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000414059	SCV000490836	pathogenic	not provided	2019-04-10	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation [or nonsense mediated decay] in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 12552571, 9809980, 16287113, 23718779, 17404884, 19727776, 17010210, 25742471, 11103790, 15863673)
Ambry Genetics	RCV000492099	SCV000580899	pathogenic	Hereditary cancer-predisposing syndrome	2023-11-09	criteria provided, single submitter	clinical testing	The c.790_793delTTTG pathogenic mutation, located in coding exon 6 of the STK11 gene, results from a deletion of 4 nucleotides at nucleotide positions 790 to 793, causing a translational frameshift with a predicted alternate stop codon (p.F264Rfs*22). This alteration has been identified in multiple cohorts of patients with a clinical diagnosis of Peutz-Jegher syndrome (Resta N et al. Cancer Res. 1998 Nov;58:4799-801; Schumacher V et al. J. Med. Genet. 2005 May;42:428-35; Thakur N et al. BMC Med. Genet. 2006 Sep;7:73; Jiang YL et al. Cancer Genet. 2019 01;230:47-57). Of note, this alteration is also designated as 787del4 in the published literature. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae	RCV000632833	SCV000754029	pathogenic	Peutz-Jeghers syndrome	2023-07-06	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 372523). This variant is also known as c.787del4. This premature translational stop signal has been observed in individual(s) with Peutz-Jeghers syndrome (PMID: 9809980, 15863673, 16287113, 17010210, 23718779, 26979979). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). 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. Loss-of-function variants in STK11 are known to be pathogenic (PMID: 15188174, 16287113).
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000414059	SCV000884613	pathogenic	not provided	2017-09-06	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000632833	SCV002057379	pathogenic	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000632833	SCV004931663	pathogenic	Peutz-Jeghers syndrome	2024-02-12	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.