ClinVar Miner

Submissions for variant NM_000314.8(PTEN):c.114T>G (p.Pro38=) (rs748040144)

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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 RCV000471003 SCV001335273 uncertain significance PTEN hamartoma tumor syndrome 2020-03-23 reviewed by expert panel curation PTEN c.114T>G (p.Pro38=) 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). No criteria currently apply to this variant.
Ambry Genetics RCV000163187 SCV000213708 likely benign Hereditary cancer-predisposing syndrome 2014-10-21 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.
GeneDx RCV000417790 SCV000534780 likely benign not specified 2016-12-06 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 RCV000471003 SCV000554527 likely benign PTEN hamartoma tumor syndrome 2020-12-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163187 SCV000691145 likely benign Hereditary cancer-predisposing syndrome 2017-10-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000417790 SCV000696528 likely benign not specified 2019-08-29 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001355014 SCV001549768 uncertain significance Malignant tumor of breast no assertion criteria provided clinical testing The PTEN p.Pro38= variant was not identified in the literature nor was it identified in the LOVD 3.0, database. The variant was identified in dbSNP (ID: rs748040144) as "With Uncertain significance allele", and ClinVar (classified as likely benign by Invitae, GeneDx, Ambry Genetics and Color; as uncertain significance by Integrated Genetics/Laboratory Corporation of America). The variant was identified in control databases in 3 of 245796 chromosomes at a frequency of 0.000012 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Latino in 1 of 33536 chromosomes (freq: 0.00003), European in 2 of 111414 chromosomes (freq: 0.000018), while the variant was not observed in the African, Other, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Pro38= 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 outside of the splicing consensus sequence and 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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