ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.945G>A (p.Pro315=) (rs376329042)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000990133 SCV000166363 benign Peutz-Jeghers syndrome 2020-12-01 criteria provided, single submitter clinical testing
GeneDx RCV000213027 SCV000171893 benign not specified 2013-11-01 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 RCV000128301 SCV000213093 likely benign Hereditary cancer-predisposing syndrome 2014-06-16 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000213027 SCV000602245 benign not specified 2017-06-16 criteria provided, single submitter clinical testing
Color Health, Inc RCV000128301 SCV000686707 likely benign Hereditary cancer-predisposing syndrome 2015-06-09 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000756723 SCV000884615 likely benign not provided 2018-04-11 criteria provided, single submitter clinical testing The p.Pro315Pro variant (rs376329042) does not alter the amino acid sequence of the STK11 protein and computational splice site prediction algorithms do not predict a change in the nearest splice site or creation of a cryptic splice site. This variant has not been reported in association with hereditary cancer in medical literature or in gene specific variation databases. This variant is listed in the Genome Aggregation Database (gnomAD) with a frequency of 0.5 percent in the Ashkenazi Jewish population (identified on 48 out of 8,990 chromosomes) and has been reported to the ClinVar database with a benign/likely benign classification (Variation ID: 135929). Based on these observations, the p.Pro315Pro variant is likely to be benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000756723 SCV000888650 benign not provided 2017-06-16 criteria provided, single submitter clinical testing
Mendelics RCV000990133 SCV001140945 likely benign Peutz-Jeghers syndrome 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000990133 SCV001285140 benign Peutz-Jeghers syndrome 2018-01-13 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000756723 SCV001747895 likely benign not provided 2021-03-01 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000213027 SCV000692053 likely benign not specified no assertion criteria provided clinical testing
True Health Diagnostics RCV000128301 SCV000788221 likely benign Hereditary cancer-predisposing syndrome 2017-12-01 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357889 SCV001553484 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The STK11 p.Pro315= variant was identified in 2 of 144 proband chromosomes (frequency: 0.01) from Spanish and Australian individuals or families with Lynch syndrome or PJS (Peutz–Jeghers syndrome (Vargas-Parra_2017_28577310, Scott_2002_12372054 ). The variant was also identified in dbSNP (ID: rs376329042) “With Likely benign allele”, ClinVar (classified benign by Invitae, GeneDx, and Quest Diagnostics Nichols Institute San Juan Capistrano, and likely benign by Ambry Genetics), Clinvitae (3x), Cosmic (1x in a carcinoma of the large intestine), Zhejiang Colon Cancer Database (8x), and in control databases in 150 of 218304 chromosomes at a frequency of 0.0007 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 3 of 19118 chromosomes (freq: 0.0002), Other in 3 of 5448 chromosomes (freq: 0.0006), Latino in 10 of 28572 chromosomes (freq: 0.0004), European Non-Finnish in 66 of 95490 chromosomes (freq: 0.0007), Ashkenazi Jewish in 48 of 8990 chromosomes (freq: 0.005), European Finnish in 2 of 20554 chromosomes (freq: 0.0001), and South Asian in 18 of 25328 chromosomes (freq: 0.0007) while not observed in the East Asian population. The variant was not identified in MutDB, LOVD 3.0, and Insight Hereditary Tumors Database The p.Pro315= 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000756723 SCV001741439 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000756723 SCV001808518 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000756723 SCV001917834 likely benign not provided no assertion criteria provided clinical testing

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