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]
Link to SEPIO compliant JSON-LD document
  • See Evidence submitted by expert panel for details.

Variant: NM_001126112.2(TP53):c.1136G>T (p.Arg379Leu)

CA338506

216463 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: f9be9559-1beb-43e6-a8cf-9eefdd968ba4
Approved on: 2021-04-02
Published on: 2021-06-16

HGVS expressions

NM_001126112.2:c.1136G>T
NM_001126112.2(TP53):c.1136G>T (p.Arg379Leu)
ENST00000269305.9:c.1136G>T
ENST00000269305.8:c.1136G>T
ENST00000359597.8:n.994-3411G>T
ENST00000413465.6:n.782+4526G>T
ENST00000420246.6:c.*243G>T
ENST00000445888.6:c.1136G>T
ENST00000455263.6:c.*155G>T
ENST00000504290.5:c.*155G>T
ENST00000504937.5:c.740G>T
ENST00000510385.5:c.*243G>T
ENST00000576024.1:n.89G>T
ENST00000610292.4:c.1019G>T
ENST00000610538.4:c.*155G>T
ENST00000610623.4:c.*155G>T
ENST00000615910.4:n.1103G>T
ENST00000617185.4:c.*243G>T
ENST00000618944.4:c.*243G>T
ENST00000619186.4:c.659G>T
ENST00000619485.4:c.1019G>T
ENST00000620739.4:c.1019G>T
ENST00000622645.4:c.*243G>T
ENST00000635293.1:c.983+954G>T
NM_000546.5:c.1136G>T
NM_001126113.2:c.*155G>T
NM_001126114.2:c.*243G>T
NM_001126115.1:c.740G>T
NM_001126116.1:c.*243G>T
NM_001126117.1:c.*155G>T
NM_001126118.1:c.1019G>T
NM_001276695.1:c.*155G>T
NM_001276696.1:c.*243G>T
NM_001276697.1:c.659G>T
NM_001276698.1:c.*243G>T
NM_001276699.1:c.*155G>T
NM_001276760.1:c.1019G>T
NM_001276761.1:c.1019G>T
NM_001276695.2:c.*155G>T
NM_001276696.2:c.*243G>T
NM_001276697.2:c.659G>T
NM_001276698.2:c.*243G>T
NM_001276699.2:c.*155G>T
NM_001276760.2:c.1019G>T
NM_001276761.2:c.1019G>T
NM_000546.6:c.1136G>T
NM_001126112.3:c.1136G>T
NM_001126113.3:c.*155G>T
NM_001126114.3:c.*243G>T
NM_001126115.2:c.740G>T
NM_001126116.2:c.*243G>T
NM_001126117.2:c.*155G>T
NM_001126118.2:c.1019G>T
NM_001276695.3:c.*155G>T
NM_001276696.3:c.*243G>T
NM_001276697.3:c.659G>T
NM_001276698.3:c.*243G>T
NM_001276699.3:c.*155G>T
NM_001276760.3:c.1019G>T
NM_001276761.3:c.1019G>T
NC_000017.11:g.7669655C>A
CM000679.2:g.7669655C>A
NC_000017.10:g.7572973C>A
CM000679.1:g.7572973C>A
NC_000017.9:g.7513698C>A
NG_017013.2:g.22896G>T

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"
Met criteria codes 4
BP4 BS3_Supporting BS2_Supporting PM2_Supporting
Not Met criteria codes 3
PS4 PM1 PM5

Evidence Links 2

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been observed in 2-7 60+ year old females without a cancer diagnosis (BS2_Supporting; internal laboratory contributor(s)). Transactivation assays show a partially functional variant according to Kato, et al. and there is no evidence of a dominant negative effect or loss of function according to Giacomelli, et al. (BS3_Supporting; PMID: 12826609, 30224644). This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 or Class C15 (BP4). In summary, TP53 c.1136G>T (p.Arg379Leu) meets criteria to be classified as likely benign for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PM2_Supporting, BS2_Supporting, BS3_Supporting, BP4.
Met criteria codes
BP4
A-GVGD: C0. BayesDel: -0.0782.
BS3_Supporting
Kato (PMID: 12826609): partially functional, Giacomelli (PMID: 30224644): noDNE+noLOF
noDNE+noLOF PubMed:30224644
partially functional PubMed:12826609
BS2_Supporting
1 female unaffected with cancer at age 60 (SCV000254625.4), 3 females unaffected with cancer at age 60 (SCV000275804.4)
PM2_Supporting
Absent from gnomAD
Not Met criteria codes
PS4
1 case meeting Revised Chompret Criteria (SCV000254625.4)
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
p.Arg379His, p.Arg379Ser, and p.Arg379Cys are VUS in ClinVar
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