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_000314.8(PTEN):c.209T>C (p.Leu70Pro)

CA000350

7826 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 12985d15-e1e7-45ab-b3e5-48e082086d4d
Approved on: 2025-12-05
Published on: 2025-12-17

HGVS expressions

NM_000314.8:c.209T>C
NM_000314.8(PTEN):c.209T>C (p.Leu70Pro)
NC_000010.11:g.87925557T>C
CM000672.2:g.87925557T>C
NC_000010.10:g.89685314T>C
CM000672.1:g.89685314T>C
NC_000010.9:g.89675294T>C
NG_007466.2:g.67119T>C
ENST00000700029.2:c.209T>C
ENST00000710265.1:c.209T>C
ENST00000472832.3:c.209T>C
ENST00000688158.2:n.944T>C
ENST00000688922.2:c.209T>C
ENST00000700021.1:c.165-5489T>C
ENST00000700022.1:c.209T>C
ENST00000700029.1:c.43T>C
ENST00000706954.1:c.209T>C
ENST00000706955.1:c.*244T>C
ENST00000686459.1:c.209T>C
ENST00000688158.1:c.*320T>C
ENST00000688308.1:c.209T>C
ENST00000688922.1:c.78T>C
ENST00000693560.1:c.728T>C
ENST00000371953.8:c.209T>C
ENST00000371953.7:c.209T>C
ENST00000498703.1:n.35T>C
ENST00000610634.1:c.107T>C
NM_000314.5:c.209T>C
NM_000314.6:c.209T>C
NM_001304717.2:c.728T>C
NM_001304718.1:c.-541-5489T>C
NM_000314.7:c.209T>C
NM_001304717.5:c.728T>C
NM_001304718.2:c.-541-5489T>C
More

Likely Pathogenic

Met criteria codes 5
PS4_Supporting PS3_Moderate PM2_Supporting PP2 PP3
Not Met criteria codes 21
PM6 PM3 PM1 PM4 PM5 PVS1 BA1 BS2 BS4 BS3 BS1 BP5 BP7 BP2 BP3 BP1 BP4 PS2 PS1 PP1 PP4

Evidence Links 0

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.209T>C (p.Leu70Pro) meets criteria to be classified as likely pathogenic 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). PS3: Phosphatase activity <50% of wild type (PMID 29706350) PM2: 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. PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (internal laboratory contributor(s) ClinVar Organization ID: 26957)
Met criteria codes
PS4_Supporting
Internal lab case ClinVar Organization ID: 26957 1 phenotype specificity point. Pt also published in 33887726
PS3_Moderate
Mighell et al data is approved for moderate weight in the truncation-like range
PM2_Supporting
Absent gnomAD v2 and v4
PP2
Missense – PP2 met – Last NT but does not appear to impact splicing (low spliceAI scores)
PP3
REVEL score 0.988
Not Met criteria codes
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
Absent gnomAD
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
Absent gnomAD
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
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
1 meiosis internal lab case ClinVar Organization ID: 26957; proband infant F with macrocephaly, variant also present in brother with macro, lipoma, dev delay
PP4
Moved to PS4. 3 internal lab cases: #1 Young adult F, eth unk, Macrocephaly, FTC dx late teens, goiter, lipoma dx 3. Min CC score = 21. #2: 40s Asian F, BrCA dx 40s, goiter dx late 20s. OFC not provided. CC score = 5. #3: Pediatric M, eth unk, Macrocephaly, lipoma, dev delay. Peds score = 5, 1 PP4 point. His baby sister with macrocephaly also positive: 1 meiosis
Curation History
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