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_000314.7(PTEN):c.685T>A (p.Ser229Thr)

CA000546

141771 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 03e612cf-a8bb-44f9-b7f8-01929aad72ec
Approved on: 2025-12-05
Published on: 2025-12-17

HGVS expressions

NM_000314.7:c.685T>A
NM_000314.7(PTEN):c.685T>A (p.Ser229Thr)
NC_000010.11:g.87957903T>A
CM000672.2:g.87957903T>A
NC_000010.10:g.89717660T>A
CM000672.1:g.89717660T>A
NC_000010.9:g.89707640T>A
NG_007466.2:g.99465T>A
ENST00000700029.2:c.685T>A
ENST00000710265.1:c.685T>A
ENST00000472832.3:c.685T>A
ENST00000688158.2:n.1420T>A
ENST00000688922.2:c.*515T>A
ENST00000700021.1:c.640T>A
ENST00000700022.1:c.*24T>A
ENST00000700023.1:n.1843T>A
ENST00000700024.1:n.2077T>A
ENST00000700025.1:n.1454T>A
ENST00000700026.1:n.322T>A
ENST00000700029.1:c.519T>A
ENST00000706954.1:c.685T>A
ENST00000706955.1:c.*720T>A
ENST00000686459.1:c.*271T>A
ENST00000688158.1:c.*796T>A
ENST00000688308.1:c.685T>A
ENST00000688922.1:c.606T>A
ENST00000693560.1:c.1204T>A
ENST00000371953.8:c.685T>A
ENST00000371953.7:c.685T>A
ENST00000472832.2:c.112T>A
NM_000314.5:c.685T>A
NM_000314.6:c.685T>A
NM_001304717.2:c.1204T>A
NM_001304718.1:c.94T>A
NM_001304717.5:c.1204T>A
NM_001304718.2:c.94T>A
NM_000314.8:c.685T>A
More

Likely Benign

Met criteria codes 5
BP5 BP4 BS1_Supporting BS3_Supporting PP2
Not Met criteria codes 19
BA1 PVS1 BP7 BP2 BP3 BS2 BS4 PP4 PP1 PP3 PM3 PM1 PM4 PM5 PM6 PS2 PS4 PS3 PS1

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.685T>A (p.Ser229Thr) is currently classified as Likely Benign 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). BS1_P: Group max filtering allele frequency of .0000044 (>.0000043) in gnomad v4. BS3_P: Score is 0.071161587 (WT-like, scores >0) (Mighel et al. 2018, PMID: 29706350). BP4: REVEL score of 0.167. Scores < 0.5 meet BP4 criteria. BP5: Two patients reported with pathogenic de novo variants in other genes that are highly correlated with the disease phenotype reported. (Internal communications) 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
Met criteria codes
BP5
Two patients reported with pathogenic de novo variants in other genes that are highly correlated with the disease phenotype reported. (Internal communications)
BP4
REVEL score of 0.167. Scores < 0.5 meet BP4 criteria.
BS1_Supporting
Group max filtering allele frequency of .0000044 (>.0000043) in gnomad v4.
BS3_Supporting
Score is 0.071161587 (WT-like, scores >0) (Mighel et al. 2018, PMID: 29706350).
PP2
PTEN classified by VCEP as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
Not Met criteria codes
BA1
Group max filtering allele frequency< 0.00056
PVS1
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
Two patients reported by GeneDx with P and LP de novo variants in other genes that could lead to phenotype, both with an unaffected parent who is Het for PTEN variant. One singleton case with LP variant in other gene that could explain phenotype, no parental testing - cannot be added to weight.
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
One unaffected homozygous individual reported by Myriad, no parental testing provided.
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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 score 0.167 < 0.75.
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
PM6
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
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
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
Curation History
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