Table 3 Variant characteristics.

From: Challenging interpretation of germline TP53 variants based on the experience of a national comprehensive cancer centre

Variant name

Variant interpretation

NCBI ClinVar

GnomAD—MAF*

NCI TP53 DB

HGVS CDNA (NM_000546.6)

HGVS protein

TP53-specific interpretation

Varsome-ACMG class

Franklin-ACMG Class

ClinGen (TP53 VCEP*)

Review status

Class

MAF total Exomes (V.2.1.1)

MAF total Genome (V.2.1.1)

TA class (transcriptional activity)

DNA LOF class

c.79C > A

p.Pro27Thr

VUS (PP3-supp; PM2-supp; PM1-supp)

VUS-LP

VUS

n.d

*

VUS(4), LB(1)

n.d

n.d

n.d

n.d

c.97-2A > C

p.?

P (PVS1-str; PM2-supp; PP3-mod; PS3-str; PS4-supp)

P

LP

n.d

n.d

no data

n.d

n.d

n.d

n.d

c.323_329dup

p.Leu111fs

LP (PVS1-str; PM2-supp)

P

P

n.d

**

P

n.d

n.d

n.d

n.d

c.375 + 6 T > C

p.?

VUS (PM2-supp; BS3-supp)

VUS-P

VUS

n.d

**

VUS

n.d

n.d

n.d

n.d

c.376-2dupA

p.?

VUS (PM2-supp; BS3-supp)

LP

LP

n.d

**

VUS

8.01E−06

n.d

n.d

n.d

c.460G > A

p.Gly154Ser

P (PS3-supp; PS4-supp; PS4-supp; PM1-str; PP3str)

P

VUS

n.d

**

VUS

3.98E−06

1,59E-04

n.d

n.d

c.466C > T

p.Arg156Cys

VUS (PM5-str; PM2-supp; BS3-supp)

P

LP

n.d

*

VUS(4), LB (3)

3.98E−06

n.d

partially functional

notDNE_notLOF

c.473G > A

p.Arg158His

P (PS3-str; PM5-str; PP3supp; PM2-supp)

P

P

n.d

**

P/LP

398E−06

n.d

non-functional

DNE_LOF

c.493C > T

p.Gln165Ter

LP (PS4-supp; PVS1-str; PM2-supp)

P

P

n.d

**

P

n.d

n.d

NA

notDNE_notLOF

c.536A > T

p.His179Leu

P (PP3-str; PM2-supp; PS4-supp; PM1-str)

P

LP

n.d

*

LP(1), VUS(1)

n.d

n.d

n.d

n.d

c.589G > C

p.Val197Leu

LP (PP3-mod; PM2-supp; PS4-mod; PM1-str)

LP

LP

n.d

*

VUS

n.d

n.d

n.d

n.d

c.614A > G

p.Tyr205Cys

LP (PM1-str, PM2-supp; PP3-str)

P

P

n.d

**

P

n.d

n.d

non-functional

DNE_LOF

c.743G > A

p.Arg248Gln

P PS3-str; PM1-str; PP3-str; PM2-supp)

P

P

P

***

P

1.19E−05

n.d

non-functional

DNE_LOF

c.764_766del

p.Ile255del

LP (PM1-str; PM2-supp; PS3-mod)

P

LP

n.d

**

LP

n.d

n.d

n.d

n.d

c.902delC

p.Pro301fs

LP (PVS1-str; PM2-supp; PS4-supp)

P

P

n.d

*

P

n.d

n.d

n.d

n.d

  1. VCEP Variant Curator Expert Panel, MAF minor allele frequency, P/LP pathogenic/likely pathogenic, VUS variant of uncertain significance, DNE dominant negative effect, LOF loss-of-function. Bold letters indicate downgrading following manual curation of interpretation using gene-specific variant interpretation criteria. In the ‘TP53-specific interpretation’ column ACMG classification criteria and evidence levels are indicated in parenthesis: str strong, supp supporting, mod moderate.
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