Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • Despite there being a valid 'cspec' property in the messages there's a discrepancy in message contents and CSPEC data: * Message Gene: PTEN CSPEC Genes: [ 'PTEN' ] * Message MONDOs: MONDO:0017623 CSPEC MONDO: []
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000314.6(PTEN):c.364A>G (p.Ile122Val)

CA000147

186161 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: c4bf5c74-cf88-47c3-812d-89a0c0e7f110
Approved on: 2025-12-05
Published on: 2025-12-17

HGVS expressions

NM_000314.6:c.364A>G
NM_000314.6(PTEN):c.364A>G (p.Ile122Val)
NC_000010.11:g.87933123A>G
CM000672.2:g.87933123A>G
NC_000010.10:g.89692880A>G
CM000672.1:g.89692880A>G
NC_000010.9:g.89682860A>G
NG_007466.2:g.74685A>G
ENST00000700029.2:c.364A>G
ENST00000710265.1:c.364A>G
ENST00000472832.3:c.364A>G
ENST00000688158.2:n.1099A>G
ENST00000688922.2:c.*194A>G
ENST00000700021.1:c.319A>G
ENST00000700022.1:c.364A>G
ENST00000700029.1:c.198A>G
ENST00000706954.1:c.364A>G
ENST00000706955.1:c.*399A>G
ENST00000686459.1:c.364A>G
ENST00000688158.1:c.*475A>G
ENST00000688308.1:c.364A>G
ENST00000688922.1:c.285A>G
ENST00000693560.1:c.883A>G
ENST00000371953.8:c.364A>G
ENST00000371953.7:c.364A>G
ENST00000498703.1:n.190A>G
ENST00000610634.1:c.262A>G
NM_000314.5:c.364A>G
NM_001304717.2:c.883A>G
NM_001304718.1:c.-387A>G
NM_000314.7:c.364A>G
NM_001304717.5:c.883A>G
NM_001304718.2:c.-387A>G
NM_000314.8:c.364A>G
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Uncertain Significance

Met criteria codes 3
BP4 PP2 PM2_Supporting
Not Met criteria codes 23
BS2 BS1 BS4 BS3 BP2 BP1 BP3 BP5 BP7 PS2 PS4 PS3 PS1 BA1 PP4 PP1 PP3 PM3 PM1 PM5 PM4 PM6 PVS1

Evidence Links 3

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PTEN Version 3.1.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.364A>G (p.Ile122Val) 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 3.1.0). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). PM2_P: Absent in large sequenced populations (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. BP4: REVEL score < 0.5 (score=0.412)
Met criteria codes
BP4
REVEL=0.412
PP2
PP2 applied because low rate of benign missense variation. I agree (FH)
PM2_Supporting
absent gnomAD I agree (FH)
Not Met criteria codes
BS2
No healthy individual reported in the literature.
BS1
Variant absent in population databases. I agree (FH)
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
Variant demonstrated lipid phosphatase activity in WT-like range (score -0.48) on high throughput phosphatase assay. PubMed:29706350
Variant demonstrated WT-like abundance on high-throughput VAMPseq assay. PubMed:29785012
Demonstrated that missense change does not affect PTEN PIP3 phosphatase activity. PubMed:21828076
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
PP2 applied because low rate of benign missense variation. I agree (FH)
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
1 individual reported in ClinVar by Ambry with limited additional information.
PS4
No reported patients in the literature and no case/control studies found.
PS3
Mighell score -0.48 but not low enough for PS3_M. In addition PMID 21828076 results conflict (WT-like). I agree (FH)
Variant demonstrated lipid phosphatase activity in WT-like range (score -0.48) on high throughput phosphatase assay. PubMed:29706350
Variant demonstrated WT-like abundance on high-throughput VAMPseq assay. PubMed:29785012
Demonstrated that missense change does not affect PTEN PIP3 phosphatase activity. PubMed:21828076
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
Variant absent in population databases. I agree (FH)
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
REVEL=0.412
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Variant does not occur within specified residues.
PM5
Not applied because variant is not at likely pathogenic.
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
1 individual reported in ClinVar by Ambry with limited additional information.
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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