Submissions for variant NM_000455.5(STK11):c.1296G>A (p.Gln432=)

gnomAD frequency: 0.00020  dbSNP: rs587781179

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000213036	SCV000171897	benign	not specified	2014-05-09	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV000128305	SCV000212873	likely benign	Hereditary cancer-predisposing syndrome	2014-07-30	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae	RCV001079439	SCV000253248	likely benign	Peutz-Jeghers syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000128305	SCV000686620	likely benign	Hereditary cancer-predisposing syndrome	2015-12-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588407	SCV000696712	benign	not provided	2017-07-06	criteria provided, single submitter	clinical testing	Variant summary: The c.1296G>A (p.Gln432=) in STK11 affects a non-conserved nucleotide and 5/5 programs in Alamut predict that this variant does not affect normal splicing. ESE finder predicts that this variant may affect multiple ESE sites. However, no functional studies confirming these predictions were published at the time of evaluation. This variant is found in 1/11504 control chromosomes of ExAC at a frequency of 0.000086 and 28/157510 chrs tested in gnomAD dataset. These frequencies exceed the maximal expected frequency of a pathogenic allele (0.0000056), suggesting this variant is benign. In addition, multiple clinical laboratories classified this variant as benign/likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, this variant was classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000588407	SCV000889853	benign	not provided	2023-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001079439	SCV001287494	uncertain significance	Peutz-Jeghers syndrome	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588407	SCV001473302	likely benign	not provided	2020-03-19	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001079439	SCV002057344	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000128305	SCV002531673	benign	Hereditary cancer-predisposing syndrome	2020-12-02	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000213036	SCV002552042	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492578	SCV004239717	likely benign	Breast and/or ovarian cancer	2023-02-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000588407	SCV004811275	likely benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	STK11: BP4, BP7, BS2
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000588407	SCV001807549	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000588407	SCV001924607	likely benign	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000588407	SCV001962790	likely benign	not provided		no assertion criteria provided	clinical testing