ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.698G>A (p.Arg233Gln) (rs770025422)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000571019 SCV000663582 uncertain significance Hereditary cancer-predisposing syndrome 2016-09-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)
ClinGen PTEN Variant Curation Expert Panel RCV000473076 SCV000930128 uncertain significance PTEN hamartoma tumor syndrome 2019-03-05 reviewed by expert panel curation PTEN c.698G>A (p.R233Q) 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: Present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort. (PMID 27535533). 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. BS3_P: In vitro or in vivo functional study or studies showing no damaging effect on protein function but BS3 not met. (PMID 29706350)
Database of Curated Mutations (DoCM) RCV000424045 SCV000507224 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434314 SCV000507225 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444322 SCV000507226 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423141 SCV000507227 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433839 SCV000507228 likely pathogenic Uterine cervical neoplasms 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444298 SCV000507229 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426398 SCV000507230 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436216 SCV000507231 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Invitae RCV000473076 SCV000541600 uncertain significance PTEN hamartoma tumor syndrome 2016-07-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 233 of the PTEN protein (p.Arg233Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs770025422, ExAC <0.01%) but has not been reported in the literature in individuals with a PTEN-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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