Patient record

VP-10321

55-64 · Female · Treatment planning

CriticalClassification drift

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

2023 · On file

Uncertain significance

Reported 14 Mar 2023

Science evolves

Today · ClinVar

Likely pathogenic

ClinVar last evaluated 18 Aug 2025 · Reviewed by expert panel

Patient summary

Record: VP-10321
Age band: 55-64
Sex: Female
Test date: 21 Aug 2023
Reporting laboratory: Partner Reference Laboratory
Ordering department: Oncology
Clinical owner: Dr. R. Okonjo
Last contact: 15 Jan 2024
Indication: Treatment planning

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

Historical finding

ClinVar

BRCA1c.5056C>T (p.His1686Tyr)

Panel: Hereditary cancer panel
Condition: Hereditary breast and ovarian cancer
ClinVar: VCV000531444
dbSNP: rs1555579648
As reported: Uncertain significance
Reported on: 14 Mar 2023

Missense change in the BRCT domain. Public submissions were limited and in agreement 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: 18 Aug 2025
Submissions: 10
Molecular consequence: missense variant
Variant type: single nucleotide variant
Location: chr17:43067626 (GRCh38)

Evidence summary

Decision support

Since the 2023 report, the consensus for BRCA1 c.5056C>T has moved from uncertain significance to likely pathogenic. That reading rests on 10 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. 4 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 retrievedBRCA1 c.5056C>T reported as Uncertain significance on 2023-03-14.
2Variant normalisedResolved to ClinVar VCV000531444 (rs1555579648) and keyed as BRCA1:c.5056C>T.
3Current evidence retrievedRead live from ClinVar: Likely pathogenic, 10 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 comparedRegional index asserts Likely pathogenic, consistent with the global reading.
6Impacted records identified12,482 findings checked; 4 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.

Global and regional evidence

Sources agree

Global · ClinVar

Likely pathogenic

reviewed by expert panel · Last evaluated 18 Aug 2025

Regional · Regional Evidence Index

Likely pathogenic

0 observations in 3,042 · updated 18 Feb 2026

Sources consistent

Both lanes fall in the same clinical band.

Both sources place this variant in the same band.

Global

Likely pathogenic

Submissions: 10
Review status: Reviewed by expert panel
Last evaluated: 18 Aug 2025
Reference frequency: Not reported

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

Regional

Likely pathogenic

Observations: 0
Cohort size: 3,042
Last updated: 18 Feb 2026
Regional frequency: 0.00e+0

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. Absent from gnomAD v4 entirely, including its ~3,000 Middle Eastern individuals. Regional data neither supports nor contradicts the expert-panel reclassification; the global reading stands.

Ancestry-informative markers and variants of uncertain significance on hereditary cancer panels. · Front Oncol 2026 · PMID 42137137
Middle Eastern Genetic Variation Improves Clinical Annotation of the Human Genome. · J Pers Med 2022 · PMID 35330423

How the interpretation changed

BRCA1 c.5056C>T. The DNA is unchanged. The evidence around it is not.

2023Genetic test performedFirst record on file carrying BRCA1 c.5056C>T.
2023Reported as uncertain significanceMissense change in the BRCT domain. Public submissions were limited and in agreement on uncertain significance at the time of reporting.
2024Further literature published2 indexed publications appeared after the original report.
2025Submissions accumulated10 independent submissions now contribute to the classification.
2025Classification now likely pathogenicLast evaluated 18 Aug 2025 · Reviewed by expert panel.
TodayVariantPulse identified the affected records4 historical records carry this variant and were flagged for clinical review.

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