Patient record

VP-10469

25-34 · Female · Early-onset malignancy

HighClassification drift

The interpretation moved across the clinically actionable boundary since this result was reported.

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

Patient summary

Record: VP-10469
Age band: 25-34
Sex: Female
Test date: 7 Feb 2023
Reporting laboratory: Partner Reference Laboratory
Ordering department: Oncology
Clinical owner: Dr. R. Okonjo
Last contact: 18 May 2023
Indication: Early-onset malignancy

Synthetic record. No identifiers in this workspace correspond to a real person.

Historical finding

ClinVar

TP53c.589G>A (p.Val197Met)

Panel: Hereditary cancer panel
Condition: Li-Fraumeni syndrome
ClinVar: VCV000188060
dbSNP: rs786204041
As reported: Uncertain significance
Reported on: 7 Feb 2023

Missense change in the DNA-binding domain. Multiple submitters agreed on uncertain significance at the time of reporting.

Current interpretation

Read from ClinVar at the last evidence sync.

Classification: Likely pathogenic
Consensus status: Reviewed by expert panel
Evidence confidence: Strong3 of 4 review criteria met
Last evaluated: 5 Dec 2025
Submissions: 11
Molecular consequence: missense variant
Variant type: single nucleotide variant
Location: chr17:7674942 (GRCh38)

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.

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.

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.

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