ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.666C>T (p.Pro222=) (rs542189325)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162395 SCV000212718 likely benign Hereditary cancer-predisposing syndrome 2014-12-09 criteria provided, single submitter clinical testing
Invitae RCV000228328 SCV000284873 benign Peutz-Jeghers syndrome 2017-10-02 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000228328 SCV000410741 likely benign Peutz-Jeghers syndrome 2016-06-14 criteria provided, single submitter clinical testing
Counsyl RCV000228328 SCV000488076 likely benign Peutz-Jeghers syndrome 2015-12-23 criteria provided, single submitter clinical testing
GeneDx RCV000423666 SCV000514796 likely benign not specified 2017-05-04 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.
Color RCV000162395 SCV000686673 benign Hereditary cancer-predisposing syndrome 2015-08-11 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000423666 SCV000920280 benign not specified 2018-04-23 criteria provided, single submitter clinical testing Variant summary: STK11 c.666C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00054 in 268862 control chromosomes, predominantly at a frequency of 0.0043 within the South Asian subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 688 fold of the estimated maximal expected allele frequency for a pathogenic variant in STK11 causing Peutz-Jeghers Syndrome phenotype (6.3e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.666C>T in individuals affected with Peutz-Jeghers Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.

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