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]
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Variant: NM_000314.6(PTEN):c.331T>C (p.Trp111Arg)

CA000401

92820 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 59486401-1daa-48dc-813f-bde6605d8cfd
Approved on: 2021-06-04
Published on: 2022-09-30

HGVS expressions

NM_000314.6:c.331T>C
NM_000314.6(PTEN):c.331T>C (p.Trp111Arg)
NC_000010.11:g.87933090T>C
CM000672.2:g.87933090T>C
NC_000010.10:g.89692847T>C
CM000672.1:g.89692847T>C
NC_000010.9:g.89682827T>C
NG_007466.2:g.74652T>C
ENST00000686459.1:c.331T>C
ENST00000688158.1:c.*442T>C
ENST00000688308.1:c.331T>C
ENST00000688922.1:n.252T>C
ENST00000693560.1:c.850T>C
ENST00000371953.8:c.331T>C
ENST00000371953.7:c.331T>C
ENST00000498703.1:n.157T>C
ENST00000610634.1:c.229T>C
NM_000314.5:c.331T>C
NM_001304717.2:c.850T>C
NM_001304718.1:c.-420T>C
NM_000314.7:c.331T>C
NM_001304717.5:c.850T>C
NM_001304718.2:c.-420T>C
NM_000314.8:c.331T>C
NM_000314.8(PTEN):c.331T>C (p.Trp111Arg)
More

Likely Pathogenic

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

Evidence Links 3

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.331T>C (p.Trp111Arg) meets criteria to be classified as likely pathogenic 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). PS3: Phosphatase activity <50% of wild type (PMID 29785012, 29706350) PM2: Absent in large sequenced populations (PMID 27535533). PS4_M: Probands with phenotype specificity score of 2-3.5. (internal laboratory contributor(s) ClinVar Organization ID: 61756, ClinVar Organization ID: 19864) 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
PS4_Moderate
Internal lab submitters Ambry (Organization ID: 61756) case with 1 phenotype specificity point; Eng lab (Organization ID: 19864) case with 1 phenotype specificity point
PS3
Protein abundance score 0.09, "low" abundance category. PubMed:29785012
Score -4.1, high confidence, truncation-like group. PubMed:29706350
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
Absent in gnomAD
Not Met criteria codes
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 in 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
PS1
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
PP4
Internal lab case: F proband in 50s endometrial ca in late 20s, IDC in 50s, nodular thyroid goiter in 30s, lung carcinoid in 50s, >10 hamartomatous colon polyps in 30s (no head circumference mentioned) - added under PS4_M Cleveland Clinic (CC) score of 31 (1 point/PP4_supporting) FHx: Sister- ADD/ADHD, redundant colon/no motility; Mother- CRC in 70s; Mat aunt- lung; MGF- CRC; MGM- lung; Father- prostate in 60s; Pat gr aunt- breast
Identified in a proband with Proteus syndrome, but no specifics on clinical features were given. PubMed:11476841
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
Absent in gnomAD
PM6
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
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
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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