Submissions for variant NM_000455.5(STK11):c.842del (p.Pro281fs)

dbSNP: rs121913321

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Pathway Genomics	RCV000172825	SCV000223791	pathogenic	Peutz-Jeghers syndrome	2014-10-30	criteria provided, single submitter	clinical testing
Invitae	RCV000172825	SCV000284878	pathogenic	Peutz-Jeghers syndrome	2023-11-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro281Argfs*6) 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: 9760200, 10353780, 17319781, 20435009). ClinVar contains an entry for this variant (Variation ID: 192227). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV000172825	SCV002057382	pathogenic	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002444692	SCV002680717	pathogenic	Hereditary cancer-predisposing syndrome	2021-06-04	criteria provided, single submitter	clinical testing	The c.842delC pathogenic mutation, located in coding exon 6 of the STK11 gene, results from a deletion of one nucleotide at nucleotide position 842, causing a translational frameshift with a predicted alternate stop codon (p.P281Rfs*6). This mutation has been detected in multiple Peutz–Jeghers syndrome (PJS) families (Nakagawa H et al. Hum Genet, 1998 Aug;103:168-72; Wang ZJ et al. J Med Genet, 1999 May;36:365-8; De Rosa M et al. Gastroenterology, 2010 Jun;138:2558-60). In addition to the clinical data presented in the 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.
Myriad Genetics, Inc.	RCV000172825	SCV004930392	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.
Key Laboratory of Carcinogenesis and Cancer Invasion, Central South University	RCV003995678	SCV004046845	likely pathogenic	Melanoma		no assertion criteria provided	clinical testing