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

UUID: 59486401-1daa-48dc-813f-bde6605d8cfd

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)

Likely Pathogenic

• Met criteria codes: PP2 PM2 PS4_Moderate PS3

• Not Met criteria codes: PP4 PP1 PP3 PM5 PM3 PM1 PM4 PM6 PVS1 BA1 BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP1 BP4 PS1 PS2

Expert Panel

PTEN VCEP

Criteria Specification Information

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

• PP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM2: Absent in gnomAD
• 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

Not Met criteria codes

• 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
• 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
• 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
• PM6: 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 in gnomAD
• 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
• BS2: 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
• 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

Approved on: 2021-06-04

Published on: 2022-09-30