ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1185A>G (p.Thr395=) (rs370207155)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000123054 SCV000166349 benign Peutz-Jeghers syndrome 2020-12-08 criteria provided, single submitter clinical testing
GeneDx RCV000213032 SCV000171895 benign not specified 2014-03-24 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 RCV000128303 SCV000212865 likely benign Hereditary cancer-predisposing syndrome 2014-06-18 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
PreventionGenetics,PreventionGenetics RCV000213032 SCV000304386 likely benign not specified criteria provided, single submitter clinical testing
Counsyl RCV000123054 SCV000488889 likely benign Peutz-Jeghers syndrome 2016-07-12 criteria provided, single submitter clinical testing
Color Health, Inc RCV000128303 SCV000686602 likely benign Hereditary cancer-predisposing syndrome 2015-03-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586467 SCV000696705 benign not provided 2017-02-09 criteria provided, single submitter clinical testing Variant summary: The c.1185A>G (p.Thr395=) in STK11 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.0004106 (31/75494 chrs tested), predominantly in individuals of European origin (0.0006144; 26/42320 chrs). The observed frequency exceeds the maximum expected allele frequency for a pathogenic variant in this gene (0.0000156), suggesting that it is a benign polymorphism. The variant was identified in at least 1 HBOC pt without strong evidence for causality. The variant of interest has been cited as Benign by multiple reputable databases/clinical laboratories. Taking together, the variant was classified as Benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586467 SCV000888637 benign not provided 2019-08-13 criteria provided, single submitter clinical testing
Mendelics RCV000123054 SCV001140948 likely benign Peutz-Jeghers syndrome 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000586467 SCV001151581 likely benign not provided 2018-05-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000123054 SCV001287491 uncertain significance Peutz-Jeghers syndrome 2018-10-09 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
True Health Diagnostics RCV000128303 SCV000788214 likely benign Hereditary cancer-predisposing syndrome 2017-09-13 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357027 SCV001552351 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The STK11 p.Thr395= variant was identified in 1 of 66 proband chromosomes (frequency: 0.02) from Australian individuals or families with Peutz–Jeghers Syndrome (Chow 2006). The variant was also identified in dbSNP (ID: rs370207155) “With other allele”, ClinVar (classified benign by Invitae, GeneDx and likely benign by Ambry Genetics, Prevention Genetics and Counsyl), Clinvitae (3x), Zhejiang Colon Cancer Database (1x), but was not identified in Cosmic, LOVD 3.0, and Insight Hereditary Tumors Database. The variant was identified in control databases in 125 of 263502 chromosomes at a frequency of 0.0005 increasing the likelihood that this may be a low frequency benign variant in certain populations of origin (Genome Aggregation Consortium Feb 27, 2017), being identified in the following populations: African in 4 of 22240 chromosomes (frequency: 0.0002), Other in 2 of 6164 chromosomes (frequency: 0.0003), Latino in 8 of 33706 chromosomes (frequency: 0.0002), European Non-Finnish in 79 of 119338 chromosomes (frequency: 0.0006),and European Finnish in 32 of 24350 chromosomes (frequency: 0.001). The p.Thr395= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000586467 SCV001809166 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000586467 SCV001921664 likely benign not provided no assertion criteria provided clinical testing

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