ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.79+7A>G (rs374331677)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000123050 SCV000886856 uncertain significance PTEN hamartoma tumor syndrome 2018-07-25 reviewed by expert panel curation PTEN c.79+7A>G (IVS1+7A>G) is currently classified as a variant of uncertain significance 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). BS3: Intronic variant with RNA, mini-gene, or other splicing assay demonstrating no splicing impact. (PMID 28677221)
GeneDx RCV000115587 SCV000149496 likely benign not specified 2017-11-22 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.
Invitae RCV000123050 SCV000166345 likely benign PTEN hamartoma tumor syndrome 2020-11-12 criteria provided, single submitter clinical testing
Color Health, Inc RCV000579577 SCV000686306 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-08 criteria provided, single submitter clinical testing This variant causes an A to G nucleotide substitution at the +7 position of intron 1 of the PTEN gene. A functional study reports no RNA defect using patient-derived cells although no data was shown (PMID: 28677221). This variant has been reported in individuals affected with Cowden or Cowden-like syndrome (PMID: 28677221). This variant has been identified in 3/251482 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000115587 SCV001362400 likely benign not specified 2019-10-11 criteria provided, single submitter clinical testing Variant summary: PTEN c.79+7A>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. One publication reports that sequencing of cDNA from patient lymphoblast cell lines with the variant resulted in no detecatble aberrations in splicing (Chen_2017). The variant allele was found at a frequency of 1.2e-05 in 251482 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.79+7A>G has been reported in the literature in individuals affected with Cowden Syndrome without strong evidence for causality (e.g. Pilarski_2011, Chen_2017). These reports do not provide unequivocal conclusions about association of the variant with Cowden Syndrome. Five laboratories have submitted clinical-significance assessments for this variant to ClinVar (evaluation after 2014) with conflicting interpretations: two laboratories cited the variant as likely benign, two cited the variant as uncertain significance, and one cited the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely benign.
Cancer Genomic Medicine Translational Research Lab,Cleveland Clinic Genomic Medicine Institute RCV000515928 SCV000579246 pathogenic Cowden syndrome 1 2017-05-26 no assertion criteria provided research

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