ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.-909T>C (rs550385924)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000758225 SCV000886860 likely benign PTEN hamartoma tumor syndrome 2018-07-25 reviewed by expert panel curation PTEN c.-909T>C (NC_000010.10:g.87863560T>C) 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). BP2: Observed in trans with a pathogenic or likely pathogenic PTEN variant. (internal laboratory contributor ClinVar Organization ID 19864) BP5: Variant found in multiple cases with alternate molecular basis for disease. (internal laboratory contributors SCV000185347.1, SCV000149485.5)
GeneDx RCV000258978 SCV000149485 uncertain significance not specified 2016-06-21 criteria provided, single submitter clinical testing This variant is denoted PTEN c.-910T>C, and describes a nucleotide substitution 910 base pairs upstream of the ATG translational start site in the PTEN promoter region. The surrounding sequence, with the base that is substituted in braces, is GTGA{T/C}GTGG. This variant, also called c.-909T>C using alternate numbering, has not been published in the literature to our knowledge. This variant was not observed at a significant allele frequency in 1000 Genomes. Variants within the PTEN promoter have been observed in individuals with features of Cowden syndrome (Zhou 2003). At this time, we consider this to be a variant of uncertain significance.
Ambry Genetics RCV000115576 SCV000185347 likely benign Hereditary cancer-predisposing syndrome 2013-10-30 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589607 SCV000889810 uncertain significance not provided 2018-03-07 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000258978 SCV001361380 likely benign not specified 2019-09-23 criteria provided, single submitter clinical testing Variant summary: PTEN c.-910T>C (also known as c.-909T>C) is located in the untranslated mRNA region upstream of the initiation codon. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 4/31172 control chromosomes at a frequency of 0.00013, which is approximately 20 times the estimated maximal expected allele frequency of a pathogenic PTEN variant (0.0000063), suggesting this variant is likely a benign polymorphism. To our knowledge, no occurrence of c.-910T>C in individuals affected with Cowden Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrence with another pathogenic variant has been reported (BRIP1 c.2078_2079delGT, p.Cys693fsX23; LCA internal database), providing supporting evidence for a benign role. Two other ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. One expert panel (ClinGen PTEN Variant Curation Expert Panel) cites this variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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