TP53c.395A>TLikely pathogenic

Print report

Variant interpretation report

TP53 c.395A>T, p.(Lys132Met)

NM_000546.6:c.395A>T NP_000537.3:p.(Lys132Met) View identifiers

Classification

Likely pathogenic

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is likely pathogenic. Select a step to read what it means.

Likely pathogenic.A likely pathogenic classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About TP53

No gene-level summary was recorded for this case.

Key facts

Condition: Li-Fraumeni syndrome
Inheritance: Autosomal dominant
Evidence used: 1 strong (pathogenic) · 1 moderate (pathogenic) · 1 supporting (pathogenic)
Expert rules: ClinGen TP53 VCEP v2.4
Other laboratories (ClinVar): 1 Pathogenic · 1 Uncertain significance
Pipeline record: 23 Jul 2026 · version 7.0.4

Evidence considered

View criteria

Applied evidence criteria

PS3 (strong): Per the TP53 VCEP Functional Worksheet (Supplementary Table S3), p.Lys132Met (K132M) is non-functional in the Kato et al. yeast-based transactivation assay and demonstrates loss of function (LOF) by the majority of other eligible functional assays (Giacomelli LOF, Kotler LOF, Kawaguchi LOF). This satisfies the VCEP PS3 rule: non-functional on Kato et al. data AND LOF by the majority of other eligible assays → PS3 at strong strength.
PM2 (supporting): The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada (allele frequency = 0). This satisfies the TP53 VCEP PM2_Supporting requirement: allele frequency <0.00003 (0.003%).
PP3 (moderate): Per the TP53 VCEP PP3-BP4-codes spreadsheet (Supplementary Table S2), c.395A>T (p.Lys132Met) is pre-assigned PP3_moderate. The variant meets VCEP PP3 moderate criteria: aGVGD Class C65 and BayesDel score 0.18419 ≥0.16, with SpliceAI max delta 0.00 (no predicted splicing impact). REVEL score 0.924 further supports a deleterious computational prediction.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.

01The reasoning

How it was classified

The recorded framework is ClinGen TP53 VCEP v2.4. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 3 Benign evidence criteria: 0

Pathogenic criteria applied · 3

PS3Strong

PS3 · strong

Per the TP53 VCEP Functional Worksheet (Supplementary Table S3), p.Lys132Met (K132M) is non-functional in the Kato et al. yeast-based transactivation assay and demonstrates loss of function (LOF) by the majority of other eligible functional assays (Giacomelli LOF, Kotler LOF, Kawaguchi LOF). This satisfies the VCEP PS3 rule: non-functional on Kato et al. data AND LOF by the majority of other eligible assays → PS3 at strong strength.

PM2Supporting

PM2 · supporting

The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada (allele frequency = 0). This satisfies the TP53 VCEP PM2_Supporting requirement: allele frequency <0.00003 (0.003%).

PP3Moderate

PP3 · moderate

Per the TP53 VCEP PP3-BP4-codes spreadsheet (Supplementary Table S2), c.395A>T (p.Lys132Met) is pre-assigned PP3_moderate. The variant meets VCEP PP3 moderate criteria: aGVGD Class C65 and BayesDel score 0.18419 ≥0.16, with SpliceAI max delta 0.00 (no predicted splicing impact). REVEL score 0.924 further supports a deleterious computational prediction.

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

Recorded classification: Likely pathogenic

ClinGen TP53 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TP53 Version 2.4 v2.4 point-based framework: PS3 strong (+4) + PM2 supporting (+1) + PP3 moderate (+2) = 7 points, which maps to Likely Pathogenic.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

gnomAD v4.1

gnomAD v2.1

Population frequency

Not recorded

gnomAD v4.1 allele counts were not recorded for this variant.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

Applied · PM2 →

gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗

SpliceAI score

0.000 maximum delta

Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · PP3 → SpliceAI ↗

ClinVar submissions

2 reported laboratory submissions

1 Pathogenic · 1 Uncertain significance. ClinVar API review status: criteria provided, conflicting classifications.

Context only ClinVar ↗

Functional evidence

Statement recorded

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.

Applied · PS3 → OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

25 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV52701687, n = 25 times).

Cancer Hotspots

This variant lies in a statistically significant hotspot.

Context only

COSMIC ↗Cancer Hotspots ↗

For specialists

Technical detail

ACMG/AMP criteria under ClinGen TP53 VCEP v2.4, with the data and sources behind each one.

27 criteria with recorded statuses: 3 met · 12 not met · 0 not assessed · 12 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM5 PM6 PP1 PP2 PP3 PP4 PP5 PS5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP3 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

PS3 (strong): p.Lys132Met is non-functional in the Kato et al. yeast transactivation assay and shows loss of function by the majority of other eligible functional assays (Giacomelli, Kotler, Kawaguchi), meeting the TP53 VCEP PS3 criteria at strong strength.

PM2_Supporting: The variant is absent from all gnomAD population databases (v2.1, v4.1, Canada), with an allele frequency of 0, satisfying the VCEP PM2_Supporting threshold of <0.00003.

PP3_Moderate: Per the VCEP PP3-BP4-codes spreadsheet, c.395A>T is pre-assigned PP3_moderate. The variant has aGVGD Class C65, BayesDel score 0.18419 (≥0.16), REVEL 0.924, and SpliceAI max delta 0.00.

Tavtigian point sum: PS3 (+4) + PM2_Supporting (+1) + PP3_Moderate (+2) = 7 points. Per TP53 VCEP v2.4 point-based rules, 6-9 points = Likely Pathogenic.

Met · 3

PS3 StrongPer the TP53 VCEP Functional Worksheet (Supplementary Table S3), p.Lys132Met (K132M) is non-functional in the Kato et al. yeast-based transactivation assay and demonstrates loss of function (LOF) by the majority of other eligible functional assays (Giacomelli LOF, Kotler LOF, Kawaguchi LOF). This satisfies the VCEP PS3 rule: non-functional on Kato et al. data AND LOF by the majority of other eligible assays → PS3 at strong strength. Details ▾Hide ▴

Evidence considered

VCEP Functional Worksheet: K132M = Non-functional (Kato)
LOF (Giacomelli)
LOF (Kotler)
LOF (Kawaguchi) → assigned PS3
Kato et al. (PMID:12826609): yeast transactivation assay of 2
314 p53 mutants
K132M non-functional
Giacomelli et al. (PMID:30224644): MITE library CRISPR screen
K132M LOF
Kotler et al. (PMID:29979965): p53 mutation library functional screen

Sources

vcep_functional_worksheetPMID:12826609 ↗PMID:30224644 ↗PMID:29979965 ↗

PM2 SupportingThe variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada (allele frequency = 0). This satisfies the TP53 VCEP PM2_Supporting requirement: allele frequency <0.00003 (0.003%). Details ▾Hide ▴

Evidence considered

gnomAD v2.1: absent (AC=0
AF=0)
gnomAD v4.1: absent (AC=0
gnomAD-Canada v1.0: absent (AC=0
Allele frequency 0 < VCEP PM2_Supporting threshold of 0.00003

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

PP3 ModeratePer the TP53 VCEP PP3-BP4-codes spreadsheet (Supplementary Table S2), c.395A>T (p.Lys132Met) is pre-assigned PP3_moderate. The variant meets VCEP PP3 moderate criteria: aGVGD Class C65 and BayesDel score 0.18419 ≥0.16, with SpliceAI max delta 0.00 (no predicted splicing impact). REVEL score 0.924 further supports a deleterious computational prediction. Details ▾Hide ▴

Evidence considered

VCEP PP3-BP4-codes: c.395A>T pre-assigned PP3_moderate
aGVGD Class C65 (pathogenic class)
BayesDel score 0.18419 ≥ 0.16 threshold
SpliceAI max delta 0.00 — no predicted splicing impact
REVEL score 0.924 — strongly predicted deleterious

Sources

vcep_pp3_bp4_codesbayesdelrevelspliceai ↗

Not met · 12 · evaluated, threshold not reached

PS2 No de novo observation data are available for this variant in the case materials. Per TP53 VCEP PS2 rules, de novo points require confirmed parentage and proband cancer type scoring; no such data were present. Details ▾Hide ▴

Still missing

No de novo proband data available for this variant
No parental confirmation or proband cancer phenotype information

PS4 No proband-level phenotype data with Li-Fraumeni syndrome cancer point scoring are available. Per TP53 VCEP PS4 rules, point scoring requires probands meeting Chompret criteria with LFS-associated cancers; no such data were present in the case materials. Details ▾Hide ▴

Still missing

No proband-level LFS cancer phenotype data available
No case-control data for allele frequency comparison

PM1 Codon 132 is not among the VCEP-specified hotspot codons (175, 245, 248, 249, 273, 282). Although the codon lies in a statistically significant hotspot per cancerhotspots.org, the exact amino acid change K132M is not listed on cancerhotspots.org and the residue does not meet the VCEP PM1 moderate threshold of ≥10 somatic occurrences for the same amino acid change. Details ▾Hide ▴

Evidence considered

Codon 132 is a statistically significant hotspot region
COSMIC: 25 somatic occurrences at this position
but exact K132M amino acid change count not specified
VCEP PM1 designated hotspot codons: 175
245
248
249
273
282 — codon 132 excluded

Still missing

Exact cancerhotspots.org count for K132M-specific somatic occurrences not available

PM5 Multiple missense variants at codon 132 are recorded in the VCEP Functional Worksheet (K132E, K132N, K132Q, K132R, K132T all assigned PS3), but none have a confirmed VCEP-classified pathogenic or likely pathogenic determination. The TP53 VCEP PM5 rule requires comparator variants to be classified as P/LP per VCEP specifications; without confirmed VCEP-classified comparators at codon 132, PM5 cannot be applied. Details ▾Hide ▴

Evidence considered

VCEP Functional Worksheet shows multiple K132 variants (K132E
K132N
K132Q
K132R
K132T) with functional LOF evidence
None of these comparators have a confirmed VCEP pathogenic/likely pathogenic classification

Still missing

VCEP classification status of comparator K132 variants (K132E
K132N
K132Q
K132R
K132T) is unknown

Sources

vcep_functional_worksheetpm5_candidates

PP1 No cosegregation data are available for this variant. Per TP53 VCEP PP1 rules, meioses must be counted in individuals carrying the variant who also have LFS-associated cancers; no such segregation data were present. Details ▾Hide ▴

Still missing

No family segregation data available
No meioses counts in variant carriers with LFS cancers

PP4 No variant allele fraction (VAF) data from patient samples are available. Per TP53 VCEP PP4 rules, the criterion requires observation of the variant with VAF 5-35% to assess somatic mosaicism; no such clinical VAF data were present. Details ▾Hide ▴

Still missing

No patient VAF data available for somatic mosaicism assessment

BA1 The variant is absent from gnomAD v2.1 and v4.1. BA1 requires a filtering allele frequency ≥0.001 (0.1%) in a continental subpopulation; the variant's AF of 0 does not meet this threshold. Details ▾Hide ▴

Evidence considered

gnomAD v2.1: AF=0
does not meet BA1 threshold of FAF ≥0.001
gnomAD v4.1: AF=0
does not meet BA1 threshold

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 The variant is absent from gnomAD v2.1 and v4.1. BS1 requires a filtering allele frequency ≥0.0003 in a continental subpopulation; the variant's AF of 0 does not meet this threshold. Details ▾Hide ▴

Evidence considered

gnomAD v2.1: AF=0
does not meet BS1 threshold of FAF ≥0.0003
gnomAD v4.1: AF=0
does not meet BS1 threshold

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS2 No data are available on cancer-free females aged ≥60 carrying this variant. Per TP53 VCEP BS2 rules, at least 2 unrelated cancer-free females ≥60 years from a single source are needed for supporting strength; no such individuals have been reported. Details ▾Hide ▴

Still missing

No data on cancer-free elderly females carrying this variant

BS3 K132M is non-functional on Kato et al. data and shows LOF across all eligible assays per the VCEP Functional Worksheet. BS3 requires functional evidence of no damaging effect (functional or partially functional on Kato AND no LOF). The variant's consistent LOF profile contradicts BS3. Details ▾Hide ▴

Evidence considered

VCEP Functional Worksheet: K132M = Non-functional (Kato)
LOF (Giacomelli
Kotler
Kawaguchi)
All functional evidence indicates loss of function
BS3 criteria are not satisfied

Sources

vcep_functional_worksheet

BS4 No segregation data are available showing lack of segregation in affected family members with LFS-associated cancers. Per TP53 VCEP BS4 rules, lack of segregation must be demonstrated in family members diagnosed with LFS cancers. Details ▾Hide ▴

Still missing

No family segregation data available

BP4 The variant is classified as aGVGD Class C65 (pathogenic) with BayesDel score 0.18419. Per TP53 VCEP BP4 rules: BP4_Moderate requires BayesDel ≤-0.008 (not met, and additionally excluded for Class C65); BP4_Supporting requires BayesDel <0.16 and >-0.008 (not met, as 0.18419 >0.16, and excluded for Class C65). No BP4 strength applies. Details ▾Hide ▴

Evidence considered

aGVGD Class C65 — BP4 expressly excluded for C65 class
BayesDel score 0.18419 >0.16 — does not meet BP4_Supporting threshold
SpliceAI max delta 0.00 — no splicing impact
but BP4 still excluded by Class C65

Sources

vcep_pp3_bp4_codesbayesdelspliceai ↗

Not applicable · 12· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/APVS1 applies only to null variants (nonsense, frameshift, canonical ±1,2 splice sites, initiation codons, CNVs) per the TP53 VCEP PVS1 flowchart. This variant is a missense substitution (p.Lys132Met) and does not qualify for PVS1. Details ▾Hide ▴

Evidence considered

Variant is a missense substitution
not a null variant per PVS1 definitions
PVS1 variant assessment confirms variant_bucket='other'
not a null variant class

Sources

vcep_pvs1_flowchartpvs1_variant_assessment

PS1 N/APS1 requires a different nucleotide change producing the same amino acid substitution (Lys132Met). K132M can only arise from c.395A>T in an AAG codon; no alternate single-nucleotide substitution produces the same K132M protein change. Details ▾Hide ▴

Evidence considered

c.395A>T is the sole single-nucleotide route to p.Lys132Met from the reference codon

PM6 VCEPThe TP53 VCEP explicitly marks PM6 as not applicable; de novo evidence is assessed under PS2 in this framework. Details ▾Hide ▴

Evidence considered

TP53 VCEP v2.4: PM6 = 'Not applicable'

PP2 VCEPThe TP53 VCEP marks PP2 as not applicable for TP53; the gene has a high rate of pathogenic missense variation and this criterion is not used. Details ▾Hide ▴

Evidence considered

TP53 VCEP v2.4: PP2 = 'Not applicable'

PP5 VCEPThe TP53 VCEP explicitly marks PP5 as 'Not Applicable for this VCEP' per ClinGen Sequence Variant Interpretation VCEP Review Committee recommendations. Details ▾Hide ▴

Evidence considered

TP53 VCEP v2.4: PP5 explicitly marked as 'Not Applicable'

BP1 VCEPThe TP53 VCEP marks BP1 as not applicable for TP53; truncating variants account for only a portion of disease-causing variants in this gene. Details ▾Hide ▴

Evidence considered

TP53 VCEP v2.4: BP1 = 'Not applicable'

BP2 VCEPThe TP53 VCEP marks BP2 as not applicable for TP53/Li-Fraumeni syndrome. Details ▾Hide ▴

Evidence considered

TP53 VCEP v2.4: BP2 = 'Not applicable'

BP3 VCEPIn-frame deletion/insertion criterion; this variant is a missense substitution. Details ▾Hide ▴

No further detail was recorded.

BP5 VCEPThe TP53 VCEP marks BP5 as not applicable; alternative molecular basis evidence is not evaluated under this code. Details ▾Hide ▴

Evidence considered

TP53 VCEP v2.4: BP5 = 'Not applicable'

BP6 VCEPThe TP53 VCEP explicitly marks BP6 as 'Not Applicable for this VCEP' per ClinGen Sequence Variant Interpretation VCEP Review Committee recommendations. ClinVar classification alone cannot be used to apply BP6 under this framework. Details ▾Hide ▴

Evidence considered

TP53 VCEP v2.4: BP6 explicitly marked as 'Not Applicable'

BP7 N/ABP7 applies to synonymous (silent) or intronic variants. This variant is a missense substitution (c.395A>T, p.Lys132Met) and does not qualify. Details ▾Hide ▴

Evidence considered

Variant is a missense substitution
not synonymous or intronic
TP53 VCEP BP7 rules are for synonymous/silent and intronic variants only

PS5 N/APS5 is not a criterion in the TP53 VCEP v2.4 framework. Under the VCEP, same-residue missense comparator evidence is assessed via PM5. Since the TP53 VCEP framework takes precedence, PS5 is not applied. Details ▾Hide ▴

Evidence considered

TP53 VCEP v2.4 does not include a PS5 criterion
PM5 serves this evidentiary role

Identifiers

Gene: TP53
Transcript: NM_000546.6
Coding (HGVS c.): NM_000546.6:c.395A>T
Protein (HGVS p.): NP_000537.3:p.(Lys132Met)
GRCh38: chr17:7675217 T>A
GRCh37: chr17:7578535 T>A
ClinVar: 376629
COSMIC: COSV52701687

Gene diagram

Every interpreted variant in TP53, mapped onto the exon structure of NM_000546.6. Select a row to find it on the plot.

TP53NM_000546.6

Fetching transcript structure from UCSC…

Exons

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Transcript span

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Strand

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Variants mapped

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Source

UCSC ncbiRefSeqCurated

All variants in TP53 — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 Allele count data not recorded

gnomAD v2.1 Allele count data not recorded

gnomAD-Canada v1.0 Allele count data not recorded

Statements

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

Pangolin splice lossmagnitude shown

-0.010

Pangolin splice gain

0.010

Other predictors

REVEL: 0.924
BayesDel: 0.296

How the predictions were used

Evidence considered

VCEP PP3-BP4-codes: c.395A>T pre-assigned PP3_moderate
aGVGD Class C65 (pathogenic class)
BayesDel score 0.18419 ≥ 0.16 threshold
SpliceAI max delta 0.00 — no predicted splicing impact
REVEL score 0.924 — strongly predicted deleterious

Sources

vcep_pp3_bp4_codesbayesdelrevelspliceai ↗

Evidence considered

aGVGD Class C65 — BP4 expressly excluded for C65 class
BayesDel score 0.18419 >0.16 — does not meet BP4_Supporting threshold
SpliceAI max delta 0.00 — no splicing impact
but BP4 still excluded by Class C65

Sources

vcep_pp3_bp4_codesbayesdelspliceai ↗

BP7 N/ABP7 applies to synonymous (silent) or intronic variants. This variant is a missense substitution (c.395A>T, p.Lys132Met) and does not qualify. Details ▾Hide ▴

Evidence considered

Variant is a missense substitution
not synonymous or intronic
TP53 VCEP BP7 rules are for synonymous/silent and intronic variants only

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.924. BayesDel score = 0.295714.

6 paper records listed. 3 cited in the classification. None of the listed paper records explicitly indicates that the variant is named.

Cited in the classification

Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.

Kato S et al. · 2003 Jul 8

Systematic site-directed mutagenesis and yeast-based functional assay of 2,314 p53 missense mutants covering all possible single-nucleotide substitutions. K132M was tested as part of the comprehensive library and classified as non-functional in the p53 transactivation assay. The per-variant data, including K132M, is captured in the VCEP Functional Worksheet (Supplementary Table S3) derived from this study.
→ PS3 Does not name this variant
PMID 12826609 ↗
Source detail

Location The variant is part of the 2,314-mutant library; individual variants are not named in the paper body. Per-variant functional results are in the VCEP Supplementary Table S3 derived from this study's data.

Context Yeast-based p53 transactivation assay using 8 p53-binding sequences (p21WAF1, MDM2, BAX, 14-3-3σ, p53AIP1, GADD45, Noxa, p53R2); also validated in Saos-2 human osteosarcoma cells via luciferase reporter assay
A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation.

Kotler E et al. · 2018 Jul 5

Created a synthetically designed p53 mutation library and measured functional impact of approximately 10,000 DNA-binding domain p53 variants. K132M was tested as part of the systematic library; the VCEP Functional Worksheet records LOF for K132M in the Kotler assay.
→ PS3 Does not name this variant
PMID 29979965 ↗
Source detail

Location Variant-level data not available in abstract; per-variant functional classification (LOF) recorded in VCEP Functional Worksheet derived from this study

Context Synthetic p53 mutation library with functional impact measurement in DBD variants
Mutational processes shape the landscape of TP53 mutations in human cancer.

Giacomelli AO et al. · 2018 Oct

Comprehensive TP53 mutagenesis by integrated tiles (MITE) library testing all missense and nonsense TP53 mutations in isogenic A549 cells. Screens for dominant-negative, loss-of-function, and WT-like alleles using nutlin-3 and etoposide. K132M was tested as part of the systematic library; the VCEP Functional Worksheet records LOF for K132M in the Giacomelli assay.
→ PS3 Does not name this variant
PMID 30224644 ↗
Source detail

Location Per-variant data in Supplementary Tables 2 and 3 (not included in the provided full text). VCEP Functional Worksheet records the LOF classification for K132M from this study.

Context CRISPR-Cas9 edited isogenic A549 lung carcinoma cells (p53 WT and p53 NULL); nutlin-3 and etoposide positive-selection screens; MITE library covering all 20 amino acids + stop at each codon

Other recorded publications

P53 mutations in Ewing's sarcoma.

Analyzed p53 deletion and sequence alterations plus MDM2 amplification in 35 Ewing's sarcoma tissue specimens. Two tumors showed p53 deletion and three had p53 mutations (codons 238, 176, 273). K132M was not identified in this study.
Does not name this variant
PMID 11295075 ↗
TP53 Variations in Human Cancers: New Lessons from the IARC TP53 Database and Genomics Data.

IARC TP53 Database overview presenting current contents and functionalities, with systematic analysis of TP53 somatic mutation data. The paper references NM_000546 as the canonical transcript and discusses TP53 mutation patterns broadly but does not discuss K132M or any individual germline variant specifically.
Does not name this variant
PMID 27328919 ↗
American College of Medical Genetics and Genomics technical standards and guidelines: microarray analysis for chromosome abnormalities in neoplastic disorders.

ACMG technical standards and guidelines for microarray analysis in neoplastic disorders. Background review paper on chromosomal microarray methodology; does not discuss TP53 variants or K132M.
Does not name this variant
PMID 23619274 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 Captured gnomAD v4.1 source record Open source ↗

gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗

SpliceAI Lookup Recorded maximum delta 0.000 Open source ↗

ClinVar 1 Pathogenic · 1 Uncertain significance Open source ↗

COSMIC Captured COSMIC source record Open source ↗

Cancer hotspots Captured Cancer Hotspots source record Open source ↗

OncoKB Captured OncoKB source record Open source ↗

ClinGen CSpec Captured ClinGen CSpec source record Open source ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Pathogenic (1 clinical laboratory) and as Uncertain significance (1 clinical laboratory). (ClinVarID = 376629)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.924. BayesDel score = 0.295714.

Functional

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.

Somatic

This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV52701687, n = 25 times).

Cancer Hotspots

This variant lies in a statistically significant hotspot.