Total submissions: 18
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clingen PTEN Variant Curation Expert Panel, |
RCV000205424 | SCV000930145 | likely benign | PTEN hamartoma tumor syndrome | 2023-08-04 | reviewed by expert panel | curation | NM_000314.8(PTEN):c.882T>G (p.Ser294Arg) meets criteria to be classified as likely benign for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (ACMG Classification Rules Specified for PTEN Variant Curation version 3.0.0). Please see a summary of the rules and criteria codes in the 'PTEN ACMG Specifications Summary' document (assertion method column). BS1: Filtering allele frequency of 0.0002887 (0.02887%, 13/24922 African/African American alleles) in gnomAD. BP4: REVEL score = 0.365. PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. Variant with benign and pathogenic codes. Classification based on application of Bayesian Classification Framework (PMID: 29300386): BS1 (-4 pts), BP4 (-1 pt), PP2 (+1 pt) = -4 pts total (Likely Benign). |
Gene |
RCV000589727 | SCV000149497 | uncertain significance | not provided | 2022-06-27 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Identified in individuals with breast or colorectal cancer (Tung 2015, Yurgelun 2017); This variant is associated with the following publications: (PMID: 23161105, 29785012, 24728327, 26800850, 28135145, 27720647, 29272070, 25186627, 33796447, 33887726, 18626510) |
Ambry Genetics | RCV000115588 | SCV000187108 | likely benign | Hereditary cancer-predisposing syndrome | 2019-06-11 | 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 | RCV000205424 | SCV000260305 | benign | PTEN hamartoma tumor syndrome | 2024-01-30 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000410224 | SCV000488210 | uncertain significance | Cowden syndrome 1 | 2016-01-22 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000589727 | SCV000602131 | likely benign | not provided | 2022-05-21 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002477278 | SCV000611428 | uncertain significance | Macrocephaly-autism syndrome; Familial meningioma; Malignant tumor of prostate; Glioma susceptibility 2; Cowden syndrome 1 | 2022-04-16 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000121909 | SCV000696544 | likely benign | not specified | 2020-10-15 | criteria provided, single submitter | clinical testing | Variant summary: PTEN c.882T>G (p.Ser294Arg) results in a non-conservative amino acid change located in the Tensin phosphatase, C2 domain (IPR014020) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 7e-05 in 283688 control chromosomes, predominantly at a frequency of 0.00052 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 33 fold of the estimated maximal expected allele frequency for a pathogenic variant in PTEN causing Hereditary Breast And Ovarian Cancer Syndrome phenotype (1.6e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.882T>G has been reported in the literature in individuals affected with neuroblastoma or colorectal cancer (Zhang_2015, Yurgelun_2017). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (6x), likely benign (2x) and benign (1x). Based on the evidence outlined above, the variant was classified as likely benign. |
Mendelics | RCV000205424 | SCV000838423 | uncertain significance | PTEN hamartoma tumor syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000115588 | SCV000910875 | likely benign | Hereditary cancer-predisposing syndrome | 2022-11-01 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000121909 | SCV002069034 | uncertain significance | not specified | 2021-06-16 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the PTEN gene demonstrated a sequence change, c.882T>G, in exon 8 that results in an amino acid change, p.Ser294Arg. This sequence change has been described in the gnomAD database with a frequency of 0.052% in the African American/African subpopulation (dbSNP rs143335584). The p.Ser294Arg change affects a moderately conserved amino acid residue located in a domain of the PTEN protein that is known to be functional. The p.Ser294Arg substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change has been reported in one individual with colorectal cancer who underwent germline genetic testing and it was considered a variant of unknown significance (PMID: 28135145). Due insufficient evidences and the lack of functional studies, the clinical significance of the p.Ser294Arg change remains unknown at this time. |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV002251985 | SCV002523647 | uncertain significance | See cases | 2020-04-07 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PP2, BP4 |
Sema4, |
RCV000115588 | SCV002528273 | likely benign | Hereditary cancer-predisposing syndrome | 2020-10-29 | criteria provided, single submitter | curation | |
Myriad Genetics, |
RCV000410224 | SCV004019896 | uncertain significance | Cowden syndrome 1 | 2023-04-05 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |
Mayo Clinic Laboratories, |
RCV000589727 | SCV004225287 | uncertain significance | not provided | 2022-12-21 | criteria provided, single submitter | clinical testing | PP2 |
Prevention |
RCV003975002 | SCV004790540 | likely benign | PTEN-related condition | 2024-01-30 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
ITMI | RCV000121909 | SCV000086113 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
Genome |
RCV003987363 | SCV004804572 | not provided | Macrocephaly-autism syndrome; Cowden syndrome 1 | no assertion provided | phenotyping only | Variant classified as Uncertain significance and reported on 11-19-2020 by USAF Medical Genetics Center. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. |