Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000314.6(PTEN):c.698G>A (p.Arg233Gln)

CA060404

376510 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 84ca1fb2-bf36-42c2-8262-5a470ed8dfa7

HGVS expressions

NM_000314.6:c.698G>A

NM_000314.6(PTEN):c.698G>A (p.Arg233Gln)

NC_000010.11:g.87957916G>A

CM000672.2:g.87957916G>A

NC_000010.10:g.89717673G>A

CM000672.1:g.89717673G>A

NC_000010.9:g.89707653G>A

NG_007466.2:g.99478G>A

ENST00000686459.1:c.*284G>A

ENST00000688158.1:c.*809G>A

ENST00000688308.1:c.698G>A

ENST00000688922.1:c.619G>A

ENST00000693560.1:c.1217G>A

ENST00000371953.8:c.698G>A

ENST00000371953.7:c.698G>A

ENST00000472832.2:c.125G>A

NM_000314.5:c.698G>A

NM_001304717.2:c.1217G>A

NM_001304718.1:c.107G>A

NM_000314.7:c.698G>A

NM_001304717.5:c.1217G>A

NM_001304718.2:c.107G>A

NM_000314.8:c.698G>A

NM_000314.8(PTEN):c.698G>A (p.Arg233Gln)

Uncertain Significance

PP2 PM2_Supporting BS3_Supporting

BP5 BP7 BP2 BP3 BP4 BP1 BA1 PP1 PP3 PM3 PM1 PM4 PM5 PM6 BS4 BS1 BS2 PS2 PS4 PS3 PS1 PVS1

Evidence Links 2

Expert Panel

PTEN VCEP

Criteria Specification Information

Criteria Specification: ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PTEN Version 3.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

PTEN VCEP

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 (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). PM2_P: 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: Well-established functional studies show no deleterious effect: Phosphatase activity >0 (score of this variant = 0.11604447) per Mighell et al. 2018 (PMID: 29706350). Using the Bayesian point system (PMID: 29300386) for this variant with conflicting evidence: 1 benign supporting and 2 pathogenic supporting codes get -1 + 1*2 points; total is 1 (Uncertain significance).

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.

PM2_Supporting

Present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort. (PMID 27535533).

BS3_Supporting

Well-established functional studies show no deleterious effect: Phosphatase activity >0 (score of this variant = 0.11604447) per Mighell et al. 2018 (PMID: 29706350).

Variant score 0.116 (WT-like range) on high throughput lipid phosphatase assay. PubMed:29706350

Variant inserted into HA1E (human epithelial kidney) cells - showed gene expression pattern similar to WT. No phosphatase/other assays done to which criteria can be applied. PubMed:27147599

BP5