Submissions for variant NM_000455.5(STK11):c.869T>C (p.Leu290Pro)

dbSNP: rs1057524439

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000434265	SCV000535560	likely pathogenic	not provided	2020-08-21	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30793491, 29399144)
CeGaT Center for Human Genetics Tuebingen	RCV000434265	SCV001371377	likely pathogenic	not provided	2020-07-01	criteria provided, single submitter	clinical testing
Invitae	RCV001362693	SCV001558723	uncertain significance	Peutz-Jeghers syndrome	2020-05-21	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has been reported to affect STK11 protein function (PMID: 29399144). This variant has been observed in individual(s) with Peutz-Jeghers syndrome (PMID: 29399144). ClinVar contains an entry for this variant (Variation ID: 392308). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 290 of the STK11 protein (p.Leu290Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline.
Genome-Nilou Lab	RCV001362693	SCV002057294	likely pathogenic	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002374723	SCV002684133	pathogenic	Hereditary cancer-predisposing syndrome	2021-09-27	criteria provided, single submitter	clinical testing	The p.L290P pathogenic mutation (also known as c.869T>C), located in coding exon 7 of the STK11 gene, results from a T to C substitution at nucleotide position 869. The leucine at codon 290 is replaced by proline, an amino acid with similar properties. This alteration has been reported in patients meeting diagnostic criteria for Peutz-Jeghers syndrome (Schneider C et al. J Clin Oncol, 2012 May;30:e140-3; Li R et al. Oncol Lett, 2018 Jan;15:717-726). This amino acid position is highly conserved in available vertebrate species. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc.	RCV001362693	SCV005084487	likely pathogenic	Peutz-Jeghers syndrome	2024-04-30	criteria provided, single submitter	clinical testing	This variant is considered likely pathogenic. This variant is expected to disrupt protein structure [Myriad internal data]. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 22493416, 29399144, 34754157].