ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.75G>A (p.Leu25=) (rs786201506)

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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 RCV000553143 SCV000840466 uncertain significance PTEN hamartoma tumor syndrome 2019-06-25 reviewed by expert panel curation PTEN c.75G>A (p.Leu25=) 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). PM2: Absent in large sequenced populations (PMID 27535533). BP7: Variant is synonymous (silent), nucleotide is not conserved, and no splicing impact is predicted.
Ambry Genetics RCV000163772 SCV000214353 likely benign Hereditary cancer-predisposing syndrome 2014-10-08 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.
Invitae RCV000553143 SCV000645620 likely benign PTEN hamartoma tumor syndrome 2019-12-31 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163772 SCV000686302 likely benign Hereditary cancer-predisposing syndrome 2015-08-11 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001358393 SCV001554111 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The PTEN p.Leu25= variant was not identified in the literature nor was it identified in the LOVD 3.0 databases. The variant was identified in dbSNP (rs786201506) as “with likely benign, uncertain significance allele” and ClinVar (classfied as likely benign by Invitae, Color and Ambry Genetics and uncertain significance by ClinGen PTEN variant panel). The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Leu25= 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. The variant occurs at a non-highly conserved nucleotide outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) 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.

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