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.599T>C (p.Phe200Ser)

CA000532

189414 (ClinVar)

Gene: PTEN (HGNC:5728)
Condition: PTEN hamartoma tumor syndrome (MONDO:0017623)
Inheritance Mode: Autosomal dominant inheritance
UUID: 633ec420-0afb-4647-b05d-ed0a118f2469
Approved on: 2025-12-05
Published on: 2025-12-17

HGVS expressions

NM_000314.8(PTEN):c.599T>C (p.Phe200Ser)
NM_000314.8:c.599T>C
NC_000010.11:g.87952224T>C
CM000672.2:g.87952224T>C
NC_000010.10:g.89711981T>C
CM000672.1:g.89711981T>C
NC_000010.9:g.89701961T>C
NG_007466.2:g.93786T>C
ENST00000700029.2:c.599T>C
ENST00000710265.1:c.599T>C
ENST00000472832.3:c.599T>C
ENST00000688158.2:n.1334T>C
ENST00000688922.2:c.*429T>C
ENST00000700021.1:c.554T>C
ENST00000700022.1:c.493-5629T>C
ENST00000700023.1:n.1757T>C
ENST00000700024.1:n.1991T>C
ENST00000700025.1:n.1368T>C
ENST00000700029.1:c.433T>C
ENST00000706954.1:c.599T>C
ENST00000706955.1:c.*634T>C
ENST00000686459.1:c.*185T>C
ENST00000688158.1:c.*710T>C
ENST00000688308.1:c.599T>C
ENST00000688922.1:c.520T>C
ENST00000693560.1:c.1118T>C
ENST00000371953.8:c.599T>C
ENST00000371953.7:c.599T>C
ENST00000472832.2:c.26T>C
NM_000314.5:c.599T>C
NM_000314.6:c.599T>C
NM_001304717.2:c.1118T>C
NM_001304718.1:c.8T>C
NM_000314.7:c.599T>C
NM_001304717.5:c.1118T>C
NM_001304718.2:c.8T>C
More

Likely Pathogenic

Met criteria codes 4
PM2 PS4_Moderate PP3 PP2
Not Met criteria codes 22
PM3 PM1 PM4 PM5 PM6 BS2 BS4 BS3 BS1 PVS1 PS2 PS3 PS1 BP5 BP7 BP2 BP3 BP4 BP1 BA1 PP4 PP1

Evidence Links 1

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.599T>C (p.Phe200Ser) 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 gnomad v4. PS4_M: Probands with phenotype specificity score of 2-3.5. (internal laboratory contributor SCV000222124.11) 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. PP3: REVEL score of 0.857, > 0.7 threshold.
Met criteria codes
PM2
Variant absent gnomAD v4.
PS4_Moderate
GDX1: child with extreme macrocephaly, DD, other neuro features, peds score = 5 = 1 PS4 point. GDX2: child with non-extreme macrocephaly, dev delay, lipoma vs. AVM, hemangioma, peds score minimum = 6 = 1 PS4 point. GDX3: child with autism, inherited from father, no other information available. No weight added.
PP3
REVEL score of 0.857, > 0.7 threshold.
PP2
PTEN is 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
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
Phe200Val at same codon, no VCEP curation, cannot apply PM5.
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
Score -3.25 BUT not high confidence - no criteria can apply. PubMed:29706350
BS1
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
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
Low confidence for cummulative functional score in Mighell et al. 2018 (PMID: 29706350).
Score -3.25 BUT not high confidence - no criteria can apply. PubMed:29706350
PS1
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
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
BP4
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
BA1
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
GDX1/Invitae/Eng lab shared family: variant present in proband with macrocephaly, dev delay, penile freck; father with macrocephaly, lipomas, hemangioma, oral papillomas, polyps and pat uncle with lipomas and polyps. Also unaffected PGM and her mother with breast cancer dx 80. Per VCEP review count 2 meioses (proband, dad, pat uncle).
Curation History
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