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.509C>T (p.Thr170Met)

CA000246

184014 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: f2fc6a36-08b0-4d07-83a2-f60e3aed090e

HGVS expressions

NM_001126112.2:c.509C>T
NM_001126112.2(TP53):c.509C>T (p.Thr170Met)
ENST00000269305.9:c.509C>T
ENST00000269305.8:c.509C>T
ENST00000359597.8:n.509C>T
ENST00000413465.6:n.509C>T
ENST00000420246.6:c.509C>T
ENST00000445888.6:c.509C>T
ENST00000455263.6:c.509C>T
ENST00000504290.5:c.113C>T
ENST00000504937.5:c.113C>T
ENST00000505014.5:n.765C>T
ENST00000509690.5:c.113C>T
ENST00000510385.5:c.113C>T
ENST00000514944.5:c.230C>T
ENST00000574684.1:n.17C>T
ENST00000610292.4:c.392C>T
ENST00000610538.4:c.392C>T
ENST00000610623.4:c.32C>T
ENST00000615910.4:n.476C>T
ENST00000617185.4:c.509C>T
ENST00000618944.4:c.32C>T
ENST00000619186.4:c.32C>T
ENST00000619485.4:c.392C>T
ENST00000620739.4:c.392C>T
ENST00000622645.4:c.392C>T
ENST00000635293.1:c.392C>T
NM_000546.5:c.509C>T
NM_001126113.2:c.509C>T
NM_001126114.2:c.509C>T
NM_001126115.1:c.113C>T
NM_001126116.1:c.113C>T
NM_001126117.1:c.113C>T
NM_001126118.1:c.392C>T
NM_001276695.1:c.392C>T
NM_001276696.1:c.392C>T
NM_001276697.1:c.32C>T
NM_001276698.1:c.32C>T
NM_001276699.1:c.32C>T
NM_001276760.1:c.392C>T
NM_001276761.1:c.392C>T
NM_001276695.2:c.392C>T
NM_001276696.2:c.392C>T
NM_001276697.2:c.32C>T
NM_001276698.2:c.32C>T
NM_001276699.2:c.32C>T
NM_001276760.2:c.392C>T
NM_001276761.2:c.392C>T
NM_000546.6:c.509C>T
NM_001126112.3:c.509C>T
NM_001126113.3:c.509C>T
NM_001126114.3:c.509C>T
NM_001126115.2:c.113C>T
NM_001126116.2:c.113C>T
NM_001126117.2:c.113C>T
NM_001126118.2:c.392C>T
NM_001276695.3:c.392C>T
NM_001276696.3:c.392C>T
NM_001276697.3:c.32C>T
NM_001276698.3:c.32C>T
NM_001276699.3:c.32C>T
NM_001276760.3:c.392C>T
NM_001276761.3:c.392C>T
NC_000017.11:g.7675103G>A
CM000679.2:g.7675103G>A
NC_000017.10:g.7578421G>A
CM000679.1:g.7578421G>A
NC_000017.9:g.7519146G>A
NG_017013.2:g.17448C>T

Likely Benign

Met criteria codes 2
BS2_Supporting BS3_Supporting
Not Met criteria codes 15
BS4 BS1 BP2 BP4 PM6 PM2 PM1 PM5 PS2 PS4 PS3 PS1 BA1 PP1 PP3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
This variant has been observed in 3 60+ year old females without a cancer diagnosis (BS2_Supporting; internal laboratory contributors). Transactivation assays show [retained/supertransactivation] function 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; PMID: 12826609, 30224644). In summary, TP53 c.509C>T (p.Thr170Met) 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: BS2_supporting; BS3_supporting.
Met criteria codes
BS2_Supporting
Variant has been seen in 3 60+ cancer free females at Ambry labs; 3 unaffected cancer free 60+ females at Invitae; 3 cancer free 60+ females at Color
BS3_Supporting
Transactivation assays show a partially functional variant according to Kato, et al. (68.4% mean transactivation activity (>20% and <=75%)) and there is no evidence of a dominant negative effect or loss of function according to Giacomelli, et al. (p53WTNutlin3 Z-score 0.108 (< 0.61) and Etoposide Z-score 1.068 (> -0.21 )) (BS3_Supporting; PMID: 12826609, 30224644)
Not Met criteria codes
BS4
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
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
This variant has a BayesDel score > 0.16 (0.3213) Align GVGD (Zebrafish) is Class 15 (PP3)
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Not met (Not selected codon (175, 248, 273, 248, 245, 282, 249) or seen in cancerhotspots.org)
PM5
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
PS4
Reported in IARC and in PMID:22653678 in a 5 year old male with embryonal rhabdomyosarcoma of the tesis at age 5 (believed to be the same case). Case not counted as we could not confirm if this was anaplastic subtype.
PS3
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
BA1
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
PP3
This variant has a BayesDel score > 0.16 (0.3213) Align GVGD (Zebrafish) is Class 15 (PP3)
Approved on: 2021-04-12
Published on: 2021-06-16
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