VP-R-2026-004

TP53 c.589G>A

Li-Fraumeni syndrome

Needs reviewHigh

Your DNA didn’t change. Science did. AI assists. Clinicians decide.

Classification change

2023 · On file

Uncertain significance

Reported 7 Feb 2023

Science evolves

Today · ClinVar

Likely pathogenic

ClinVar last evaluated 5 Dec 2025 · Reviewed by expert panel

The DNA has not changed. Only the interpretation has.TP53 c.589G>A (p.Val197Met) · identical in both

Classification drift

Variant

Gene: TP53
HGVS (coding): c.589G>A
Protein: p.Val197Met
ClinVar: VCV000188060
dbSNP: rs786204041
Panel: Hereditary cancer panel
Molecular consequence: missense variant

How the interpretation changed

TP53 c.589G>A. The DNA is unchanged. The evidence around it is not.

2023Genetic test performedFirst record on file carrying TP53 c.589G>A.
2023Reported as uncertain significanceMissense change in the DNA-binding domain. Multiple submitters agreed on uncertain significance at the time of reporting.
2025Submissions accumulated11 independent submissions now contribute to the classification.
2025Classification now likely pathogenicLast evaluated 5 Dec 2025 · Reviewed by expert panel.
TodayVariantPulse identified the affected records2 historical records carry this variant and were flagged for clinical review.

Evidence summary draft

AI draft · clinician must review

Evidence summary

Decision support

Since the 2023 report, the consensus for TP53 c.589G>A has moved from uncertain significance to likely pathogenic. That reading rests on 11 submissions at strong review confidence, reviewed by expert panel. That crosses the clinically actionable boundary, so management guidance issued on the original interpretation may no longer be the right guidance. 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.

Patient impact

The changed variant and every historical record that carries it. Select a record to see its detail.

Synthetic demonstration data

Changed variant

TP53

c.589G>A

VUSLikely pathogenic

VP-10469

Not reviewed

25-34 · Oncology

Synthetic ID: VP-10469
Test date: 7 Feb 2023
Original classification: Uncertain significancereported 7 Feb 2023
Current evidence: Likely pathogenicClinVar, evaluated 5 Dec 2025
Clinical owner: Dr. R. Okonjo
Review status: Not reviewed

Open record

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
ClinVar11 submissions on record.	Likely pathogenic	Reviewed by expert panel	5 Dec 2025	Strong3 of 4 review criteria met	VCV000188060
Population frequencyHighest reported allele frequency carried on the source record.	Not reported	No frequency data	5 Dec 2025	Reference observation
LiteraturePublications linked to this variant record.	8 indexed publications	PubMed index	Latest 2022	Supporting context
Regional Evidence IndexModelled regional aggregation maintained inside this workspace	No regional record	Not held	-	-
This institutionThe interpretation issued to the patient at the time of testing.	Uncertain significance	Internal report	7 Feb 2023	On record

Cited publications

ACMG SF v3.1 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG). · Genet Med 2022 · PMID 35802134
Standards for the classification of pathogenicity of somatic variants in cancer (oncogenicity): Joint recommendations of Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC), and Variant Interpretation for Cancer Consortium (VICC). · Genet Med 2022 · PMID 35101336
Chromosomal microarray analysis, including constitutional and neoplastic disease applications, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG). · Genet Med 2021 · PMID 34131312
ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). · Genet Med 2021 · PMID 34012068
Clinical Features of Breast Cancer in South Korean Patients with Germline TP53 Gene Mutations. · J Breast Cancer 2021 · PMID 33818021
TP53 variants of uncertain significance: increasing challenges in variant interpretation and genetic counseling. · Fam Cancer 2019 · PMID 31321604
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

How VariantPulse reached this resultEight steps, each one inspectable

1Historical record retrievedTP53 c.589G>A reported as Uncertain significance on 2023-02-07.
2Variant normalisedResolved to ClinVar VCV000188060 (rs786204041) and keyed as TP53:c.589G>A.
3Current evidence retrievedRead live from ClinVar: Likely pathogenic, 11 submissions, reviewed by expert panel.
4Classification difference detectedRecorded interpretation normalised to Uncertain significance. Current interpretation normalised to Likely pathogenic. The interpretation crossed into the clinically actionable band, so records carrying it may need review.
5Regional sources comparedNo regional evidence is held for this variant.
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.

+60Moved into the actionable bandUncertain significance to Likely pathogenic.
+102 records on fileHistorical results carrying this variant that a reviewer would reassess.
+10High review confidenceThe current classification carries expert-panel or guideline review.

Ordering score80

Case trail

Every review action on this case, with who took it and when.

No review actions on this case yet.

Recommendation

Reassess 2 records against the current interpretation and decide whether the reporting clinician should be notified. Final interpretation remains with the clinical team.

Review actions

Each action is recorded in the audit trail. None changes a classification or a diagnosis.

Assign reviewer

Clinician note

Decision

A decision needs a clinician note of at least 10 characters. It records the outcome of the review; it does not write to any patient record or issue a diagnosis.

Case detail

Case: VP-R-2026-004
Raised: 1m ago
Assigned: Unassigned
Evidence source: ClinVar · Evidence monitor live
Records impacted: 2

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

Affected records in full

Synthetic demonstration data

Record	Age band	Test date	As reported	Current	Department	Clinical owner	Last contact	Review state
VP-10469	25-34	7 Feb 2023	VUS	Likely pathogenic	Oncology	Dr. R. Okonjo	3y ago	Not reviewed
VP-10506	5-11	25 Jul 2023	VUS	Likely pathogenic	Clinical Genetics	Dr. M. Suleiman	3y ago	Not reviewed

Source

Classification

Review level

Last updated

Strength

ClinVar11 submissions on record.

Likely pathogenic

Reviewed by expert panel

5 Dec 2025

Strong

VCV000188060

Population frequencyHighest reported allele frequency carried on the source record.

Not reported

No frequency data

5 Dec 2025

Reference observation

LiteraturePublications linked to this variant record.

8 indexed publications

PubMed index

Latest 2022

Supporting context

Regional Evidence IndexModelled regional aggregation maintained inside this workspace

No regional record

Not held

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

Uncertain significance

Internal report

7 Feb 2023

On record

Record

Age band

Test date

As reported

Current

Department

Clinical owner

Last contact

Review state

VP-10469

25-34

7 Feb 2023

VUS

Likely pathogenic

Oncology

Dr. R. Okonjo

3y ago

Not reviewed

VP-10506

5-11

25 Jul 2023

VUS

Likely pathogenic

Clinical Genetics

Dr. M. Suleiman

3y ago

Not reviewed