Hereditary cancer panel

TP53 c.440T>G

p.Val147Gly · Li-Fraumeni syndrome

Evidence strengthenedMediumVP-R-2026-004VCV003602769

Then and now

The interpretation moved further toward pathogenicity without crossing a band boundary.

Then2023

Likely pathogenic

As reported

Science
changed

Now2025

Pathogenic

Multiple submitters, no conflicts

Evidence summary

Decision support

Evidence for TP53 c.440T>G has firmed up since the 2023 report: the consensus moved from likely pathogenic to pathogenic on the strength of 2 submissions. The clinical band is unchanged, so this is a confidence shift rather than a reversal. 2 records on file carry this variant and have not yet been reassessed.

Composed from the structured fields of the records cited on this page. Requires clinical verification before it informs any decision.

Evidence by source

Each source is shown as it reports itself. VariantPulse does not merge them into a single verdict.

Source	Classification	Review level	Last updated	Strength
ClinVar2 submissions on record.	Pathogenic	Multiple submitters, no conflicts	7 Oct 2025	Moderate2 of 4 review criteria met	VCV003602769
Population frequencyHighest reported allele frequency carried on the source record.	Not reported	No frequency data	7 Oct 2025	Reference observation
LiteraturePublications linked to this variant record.	8 indexed publications	PubMed index	Latest 2018	Supporting context
Regional Evidence IndexModelled regional aggregation maintained inside this workspace	Pathogenic	2 regional observations	27 Feb 2026	Cohort 5,400
This institutionThe interpretation issued to the patient at the time of testing.	Likely pathogenic	Internal report	2 Sept 2023	On record

Cited publications

Mutational processes shape the landscape of TP53 mutations in human cancer. — Nat Genet 2018 · PMID 30224644
A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation. — Mol Cell 2018 · PMID 29979965
Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional Version. — National Cancer Institute (US) 2002 · PMID 26389258
Genetics of Breast and Gynecologic Cancers (PDQ®): Health Professional Version. — National Cancer Institute (US) 2002 · PMID 26389210
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. — Genet Med 2015 · PMID 25741868
A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. — Genet Med 2015 · PMID 25394175
American Society of Clinical Oncology Expert Statement: collection and use of a cancer family history for oncology providers. — J Clin Oncol 2014 · PMID 24493721
Li-Fraumeni Syndrome. — University of Washington, Seattle 1993 · PMID 20301488

Global and regional evidence

Sources agree

Global

Pathogenic

Submissions: 2
Review status: Multiple submitters, no conflicts
Last evaluated: 7 Oct 2025
Reference frequency: Not reported

Read from ClinVar, which aggregates submissions dominated by European-ancestry cohorts.

Regional

Pathogenic

Observations: 2
Cohort size: 5,400
Last updated: 27 Feb 2026
Regional frequency: 1.80e-4

Modelled regional aggregation maintained inside this workspace.

VariantPulse analysis

Both sources place this variant in the same band, so there is no divergence to resolve. Regional cohorts agree with the global classification.

How the interpretation changed

TP53 c.440T>G — the DNA is unchanged. The evidence around it is not.

2023Genetic test performedFirst record on file carrying TP53 c.440T>G.
2023Reported as likely pathogenicDNA-binding domain missense change with supportive functional assay data. Reported as likely pathogenic pending further submissions.
2025Submissions accumulated2 independent submissions now contribute to the classification.
2025Classification now pathogenicLast evaluated 7 Oct 2025 · Multiple submitters, no conflicts.
TodayVariantPulse identified the affected records2 historical records carry this variant and were flagged for clinical review.

How VariantPulse reached this resultEight steps, each one inspectable

1Historical record retrievedTP53 c.440T>G reported as Likely pathogenic on 2023-09-02.
2Variant normalisedResolved to ClinVar VCV003602769 and keyed as TP53:c.440T>G.
3Current evidence retrievedRead live from ClinVar: Pathogenic/Likely pathogenic, 2 submissions, criteria provided, multiple submitters, no conflicts.
4Classification difference detectedRecorded interpretation normalised to Likely pathogenic. Current interpretation normalised to Pathogenic. Evidence moved toward pathogenicity within the same band.
5Regional sources comparedRegional index asserts Pathogenic, consistent with the global reading.
6Impacted records identified12,482 findings checked; 2 carry this variant.
7Evidence brief generatedComposed from the structured fields of the cited records above.
8Human review requestedVariantPulse does not change any record. A clinician decides what happens next.

Review priority

A triage signal for the queue. Not a clinical risk score, and not a statement about any individual.

+20Evidence strengthenedCurrent evidence supports the interpretation more firmly than before.
+102 records on fileHistorical results carrying this variant that a reviewer would reassess.

Ordering score30

Records carrying this variant

Historical findings in the connected record system that reference this variant.

Record	Age band	Test date	As reported	Current	Department	Clinical owner	Last contact	Review state
VP-11290	35-44	2 Sept 2023	Likely pathogenic	Pathogenic	Oncology	Dr. R. Okonjo	3y ago	Not reviewed
VP-11317	18-24	14 Oct 2023	Likely pathogenic	Pathogenic	Clinical Genetics	Dr. M. Suleiman	3y ago	Not reviewed

Recommendation

Confirm whether the strengthened evidence changes management for 2 records. The clinical band is unchanged.

Decision support only. Final interpretation remains with the qualified clinical team.

Source

Classification

Review level

Last updated

Strength

ClinVar2 submissions on record.

Pathogenic

Multiple submitters, no conflicts

7 Oct 2025

Moderate

VCV003602769

Population frequencyHighest reported allele frequency carried on the source record.

Not reported

No frequency data

7 Oct 2025

Reference observation

LiteraturePublications linked to this variant record.

8 indexed publications

PubMed index

Latest 2018

Supporting context

Regional Evidence IndexModelled regional aggregation maintained inside this workspace

Pathogenic

2 regional observations

27 Feb 2026

Cohort 5,400

This institutionThe interpretation issued to the patient at the time of testing.

Likely pathogenic

Internal report

2 Sept 2023

On record

Record

Age band

Test date

As reported

Current

Department

Clinical owner

Last contact

Review state

VP-11290

35-44

2 Sept 2023

Likely pathogenic

Pathogenic

Oncology

Dr. R. Okonjo

3y ago

Not reviewed

VP-11317

18-24

14 Oct 2023

Likely pathogenic

Pathogenic

Clinical Genetics

Dr. M. Suleiman

3y ago

Not reviewed