VP-R-2026-013

TP53 c.784G>A

Li-Fraumeni syndrome

Needs reviewLow

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

Classification change

2022 · On file

Uncertain significance

Reported 13 Sept 2022

Science evolves

Today · ClinVar

Likely benign

ClinVar last evaluated 3 Apr 2025 · Reviewed by expert panel

The DNA has not changed. Only the interpretation has.TP53 c.784G>A (p.Gly262Ser) · identical in both

Evidence weakened

Variant

Gene: TP53
HGVS (coding): c.784G>A
Protein: p.Gly262Ser
ClinVar: VCV000141228
dbSNP: rs200579969
Panel: Hereditary cancer panel
Molecular consequence: missense variant

How the interpretation changed

TP53 c.784G>A. The DNA is unchanged. The evidence around it is not.

2022Genetic test performedFirst record on file carrying TP53 c.784G>A.
2022Reported as uncertain significanceReported as uncertain significance by expert-panel criteria at the time.
2025Submissions accumulated13 independent submissions now contribute to the classification.
2025Classification now likely benignLast evaluated 3 Apr 2025 · Reviewed by expert panel.
TodayVariantPulse identified the affected recordsOne historical record carries this variant and was flagged for clinical review.

Evidence summary draft

AI draft · clinician must review

Evidence summary

Decision support

Accumulated evidence now favours a more benign reading of TP53 c.784G>A than the uncertain significance interpretation issued in 2022; the current consensus is likely benign. Where the original result drove additional testing or surveillance, that basis may have weakened. One record on file carries this variant and has 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.784G>A

VUSLikely benign

VP-10839

Not reviewed

55-64 · Oncology

Synthetic ID: VP-10839
Test date: 13 Sept 2022
Original classification: Uncertain significancereported 13 Sept 2022
Current evidence: Likely benignClinVar, evaluated 3 Apr 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
ClinVar13 submissions on record.	Likely benign	Reviewed by expert panel	3 Apr 2025	Strong3 of 4 review criteria met	VCV000141228
Population frequencyHighest reported allele frequency carried on the source record.	2.00e-5	The Genome Aggregation Database (gnomAD)	3 Apr 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	13 Sept 2022	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
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
Returning Individual Genetic Research Results to Research Participants: Uptake and Outcomes Among Patients With Breast Cancer. · JCO Precis Oncol 2018 · PMID 32095738
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
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. · Genet Med 2017 · PMID 28492532
Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. · Genet Med 2017 · PMID 27854360
Targeted massively parallel sequencing of a panel of putative breast cancer susceptibility genes in a large cohort of multiple-case breast and ovarian cancer families. · J Med Genet 2016 · PMID 26534844

How VariantPulse reached this resultEight steps, each one inspectable

1Historical record retrievedTP53 c.784G>A reported as Uncertain significance on 2022-09-13.
2Variant normalisedResolved to ClinVar VCV000141228 (rs200579969) and keyed as TP53:c.784G>A.
3Current evidence retrievedRead live from ClinVar: Likely benign, 13 submissions, reviewed by expert panel.
4Classification difference detectedRecorded interpretation normalised to Uncertain significance. Current interpretation normalised to Likely benign. Evidence moved toward a benign interpretation.
5Regional sources comparedNo regional evidence is held for this variant.
6Impacted records identified12,482 findings checked; 1 carries 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.

+10Evidence weakenedCurrent evidence favours a more benign reading than the one on record.
+51 record on fileHistorical results carrying this variant that a reviewer would reassess.
+10High review confidenceThe current classification carries expert-panel or guideline review.

Ordering score25

Case trail

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

No review actions on this case yet.

Recommendation

Review whether surveillance driven by the original interpretation is still indicated for 1 record.

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-2026-013
Raised: 1m ago
Assigned: Unassigned
Evidence source: ClinVar · Evidence monitor live
Records impacted: 1

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-10839	55-64	13 Sept 2022	VUS	Likely benign	Oncology	Dr. R. Okonjo	4y ago	Not reviewed

Source

Classification

Review level

Last updated

Strength

ClinVar13 submissions on record.

Likely benign

Reviewed by expert panel

3 Apr 2025

Strong

VCV000141228

Population frequencyHighest reported allele frequency carried on the source record.

2.00e-5

The Genome Aggregation Database (gnomAD)

3 Apr 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

13 Sept 2022

On record

Record

Age band

Test date

As reported

Current

Department

Clinical owner

Last contact

Review state

VP-10839

55-64

13 Sept 2022

VUS

Likely benign

Oncology

Dr. R. Okonjo

4y ago

Not reviewed