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
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000546.6(TP53):c.1179dup (p.Ter394LeuextTer?)

CA645369640

428888 (ClinVar)

Gene: TP53 (HGNC:7157)
Condition: Li-Fraumeni syndrome (MONDO:0018875)
Inheritance Mode: Autosomal dominant inheritance
UUID: 06436fd1-ae1e-4dce-a733-08246ea94d07
Approved on: 2025-12-05
Published on: 2025-12-05

HGVS expressions

NM_000546.6(TP53):c.1179dup (p.Ter394LeuextTer?)
NM_000546.6:c.1179dup
NC_000017.11:g.7669612dup
CM000679.2:g.7669612dup
NC_000017.10:g.7572930dup
CM000679.1:g.7572930dup
NC_000017.9:g.7513655dup
NG_017013.2:g.22939dup
ENST00000503591.2:c.1179dup
ENST00000508793.6:c.1179dup
ENST00000509690.6:c.783dup
ENST00000514944.6:c.900dup
ENST00000604348.6:c.1158dup
ENST00000269305.9:c.1179dup
ENST00000269305.8:c.1179dup
ENST00000359597.8:c.994-3368dup
ENST00000413465.6:c.782+4569dup
ENST00000420246.6:c.*286dup
ENST00000445888.6:c.1179dup
ENST00000455263.6:c.*198dup
ENST00000504290.5:c.*198dup
ENST00000504937.5:c.783dup
ENST00000510385.5:c.*286dup
ENST00000576024.1:c.132dup
ENST00000610292.4:c.1062dup
ENST00000610538.4:c.*198dup
ENST00000610623.4:c.*198dup
ENST00000615910.4:c.1146dup
ENST00000617185.4:c.*286dup
ENST00000618944.4:c.*286dup
ENST00000619186.4:c.702dup
ENST00000619485.4:c.1062dup
ENST00000620739.4:c.1062dup
ENST00000622645.4:c.*286dup
ENST00000635293.1:c.983+997dup
NM_000546.5:c.1179dup
NM_001126112.2:c.1179dup
NM_001126113.2:c.*198dup
NM_001126114.2:c.*286dup
NM_001126115.1:c.783dup
NM_001126116.1:c.*286dup
NM_001126117.1:c.*198dup
NM_001126118.1:c.1062dup
NM_001276695.1:c.*198dup
NM_001276696.1:c.*286dup
NM_001276697.1:c.702dup
NM_001276698.1:c.*286dup
NM_001276699.1:c.*198dup
NM_001276760.1:c.1062dup
NM_001276761.1:c.1062dup
NM_001276695.2:c.*198dup
NM_001276696.2:c.*286dup
NM_001276697.2:c.702dup
NM_001276698.2:c.*286dup
NM_001276699.2:c.*198dup
NM_001276760.2:c.1062dup
NM_001276761.2:c.1062dup
NM_001126112.3:c.1179dup
NM_001126113.3:c.*198dup
NM_001126114.3:c.*286dup
NM_001126115.2:c.783dup
NM_001126116.2:c.*286dup
NM_001126117.2:c.*198dup
NM_001126118.2:c.1062dup
NM_001276695.3:c.*198dup
NM_001276696.3:c.*286dup
NM_001276697.3:c.702dup
NM_001276698.3:c.*286dup
NM_001276699.3:c.*198dup
NM_001276760.3:c.1062dup
NM_001276761.3:c.1062dup
More

Likely Pathogenic

Met criteria codes 3
PVS1_Moderate PS2 PM2
Not Met criteria codes 11
BS4 BS3 BS1 BS2 BP2 PS4 PS3 BA1 PP4 PP1 PM3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen TP53 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TP53 Version 2.3.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
The NM_000546.6 c.1179dup (p.Ter394LeuextTer76) is a TP53 frameshift variant introducing a C-terminal extension of 76 residues in the protein (PVS1_Moderate). This variant has been identified as a de novo occurrence with confirmed parental relationships in 1 individual with a strongly LFS-associated cancer totaling 4 phenotype points (PS2_Strong; ClinVar SCV000581133.6 and SCV003327690.3, Internal lab contributors). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as likely pathogenic for Li Fraumeni syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen TP53 VCEP: PVS1_Moderate, PS2_Strong, PM2_Supporting. (Bayesian Points: 7; VCEP specifications version 2.3)
Met criteria codes
PVS1_Moderate
The NM_000546.6 c.1179dup (p.Ter394LeuextTer76) is a TP53 frameshift variant introducing a C-terminal extension of 76 residues in the protein (PVS1_Moderate; PMIDs).
PS2
This variant has been identified as a de novo occurrence with confirmed parental relationships in 1 individual with a strongly LFS-associated cancer totaling 4 phenotype points (PS2_Strong; ClinVar SCV000581133.6 and SCV003327690.3, Internal lab contributors).
PM2
This variant is absent from gnomAD v4.1.0 (PM2_Supporting).
Not Met criteria codes
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
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
BP2
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
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
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
Curation History
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