ClinVar Miner

Submissions for variant NM_001126049.1(KLLN):c.-840G>A (rs563841270)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000233564 SCV000863474 likely benign PTEN hamartoma tumor syndrome 2018-04-06 reviewed by expert panel curation PTEN c.-1142C>T (NC_000010.10:g.89623084C>T) meets criteria to be classified as likely benign for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the "PTEN ACMG Specifications Summary" document (assertion method column). BS1: Allele frequency of 0.0049 (0.49%, 8/1622 alleles) in the East Asian subpopulation of the gnomAD cohort. (PMID 27535533) BP2: Observed in trans with a pathogenic or likely pathogenic PTEN variant, at least three observations in cis and/or phase unknown with different pathogenic/likely pathogenic PTEN variants. (Internal laboratory contributors SCV000187279.1, SCV000149465.6)
GeneDx RCV000201311 SCV000149465 likely benign not specified 2016-06-08 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 RCV000115556 SCV000187279 uncertain significance Hereditary cancer-predisposing syndrome 2014-03-10 criteria provided, single submitter clinical testing
Invitae RCV000233564 SCV000284571 likely benign PTEN hamartoma tumor syndrome 2016-03-18 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590028 SCV000696527 likely benign not provided 2017-01-20 criteria provided, single submitter clinical testing Variant summary: The PTEN variant c.-1142C>T (also known as c.-1143C>T) located in the 5' UTR region of PTEN causes an alteration of a non-conserved nucleotide. The variant of interest was observed in the 1000 Gs control population with an allele frequency of 12/5044 (1/420, 1 homozygote), predominantly in the East Asian cohort, 8/1008 (1/125, 1 homozygote), which exceeds the estimated maximal expected allele frequency for a pathogenic PTEN variant of 1/158730. Therefore, suggesting this variant is likely a benign polymorphism for in population(s) of East Asian origin. However, these observations do need to be cautiously considered due to the PTEN pseudogene possibly being captured. A functional study, Ohsaka_2010, found the variant not to affect luciferase activity, although they do state the outcome is cell type dependent. In addition, multiple clinical diagnostic laboratories classified this variant as "likely benign" or "uncertain significance." Therefore, the variant of interest has been classified as "likely benign."
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000590028 SCV000888582 benign not provided 2018-06-19 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000201311 SCV000691986 uncertain significance not specified no assertion criteria provided clinical testing

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