Hereditary cancer panel

BRCA1 c.5123C>T

p.Ala1708Val · Hereditary breast and ovarian cancer

Consensus conflictMediumVP-R-2026-011VCV000037640 rs28897696

Then and now

Submitters no longer agree on how this variant should be classified.

2022 · On file

Uncertain significance

Reported 21 Nov 2022

Science evolves

Today · ClinVar

Conflicting classifications

ClinVar last evaluated 31 Jan 2026 · Conflicting submissions

The DNA has not changed. Only the interpretation has.BRCA1 c.5123C>T (p.Ala1708Val) · identical in both

Patient impact

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

Synthetic demonstration data

Changed variant

BRCA1

c.5123C>T

VUSConflicting

VP-10876

Not reviewed

35-44 · Clinical Genetics

Synthetic ID: VP-10876
Test date: 21 Nov 2022
Original classification: Uncertain significancereported 21 Nov 2022
Current evidence: Conflicting classificationsClinVar, evaluated 31 Jan 2026
Clinical owner: Dr. M. Suleiman
Review status: Not reviewed

Open record

Evidence summary

Decision support

Submitters no longer agree on BRCA1 c.5123C>T. The 2022 report recorded uncertain significance, and current submissions are split rather than resolving to a single classification. A conflicting record is not the same as a benign one, and it is not the same as a pathogenic one. 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.

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
ClinVar25 submissions on record.	Conflicting classifications	Conflicting submissions	31 Jan 2026	Limited1 of 4 review criteria met	VCV000037640
Population frequencyHighest reported allele frequency carried on the source record.	0.00023	NHLBI Exome Sequencing Project (ESP) Exome Variant Server	31 Jan 2026	Reference observation
LiteraturePublications linked to this variant record.	8 indexed publications	PubMed index	Latest 2024	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	21 Nov 2022	On record

Cited publications

ATM-Related Cancer Predisposition. · University of Washington, Seattle 1993 · PMID 42258614
Evidence-based recommendations for gene-specific ACMG/AMP variant classification from the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel. · Am J Hum Genet 2024 · PMID 39142283
Defining and Reducing Variant Classification Disparities. · medRxiv 2024 · PMID 38645101
BRCA1 and BRCA2 mutations and their clinical relevance in selected women diagnosed with triple-negative breast cancer in Kenya: a descriptive cross-sectional study. · Pan Afr Med J 2023 · PMID 37719058
Functional analyses of rare germline BRCA1 variants by transcriptional activation and homologous recombination repair assays. · BMC Cancer 2023 · PMID 37085799
The germline mutational landscape of genitourinary cancers and its indication for prognosis and risk. · BMC Urol 2022 · PMID 36451132
Germline variants profiling of BRCA1 and BRCA2 in Chinese Hakka breast and ovarian cancer patients. · BMC Cancer 2022 · PMID 35918668
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

How the interpretation changed

BRCA1 c.5123C>T. The DNA is unchanged. The evidence around it is not.

2022Genetic test performedFirst record on file carrying BRCA1 c.5123C>T.
2022Reported as uncertain significanceMissense change in the BRCT domain. Submitters agreed on uncertain significance at the time of reporting.
2023Further literature published4 indexed publications appeared after the original report.
2026Submissions accumulated25 independent submissions now contribute to the classification.
2026Classification now conflicting classificationsLast evaluated 31 Jan 2026 · Conflicting submissions.
TodayVariantPulse identified the affected recordsOne historical record carries this variant and was flagged for clinical review.

How VariantPulse reached this resultEight steps, each one inspectable

1Historical record retrievedBRCA1 c.5123C>T reported as Uncertain significance on 2022-11-21.
2Variant normalisedResolved to ClinVar VCV000037640 (rs28897696) and keyed as BRCA1:c.5123C>T.
3Current evidence retrievedRead live from ClinVar: Conflicting classifications of pathogenicity, 25 submissions, criteria provided, conflicting classifications.
4Classification difference detectedRecorded interpretation normalised to Uncertain significance. Current interpretation normalised to Conflicting classifications. Current submissions disagree, so no single consensus exists.
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.

+30Submitters disagreeNo single consensus classification is available.
+51 record on fileHistorical results carrying this variant that a reviewer would reassess.
-5Limited review confidenceThe current classification rests on a narrow submission base.

Ordering score30

Records carrying this variant

The same records as a list, for scanning and screen readers.

Synthetic demonstration data

Record	Age band	Test date	As reported	Current	Department	Clinical owner	Last contact	Review state
VP-10876	35-44	21 Nov 2022	VUS	Conflicting	Clinical Genetics	Dr. M. Suleiman	4y ago	Not reviewed

Recommendation

Manual review recommended: no single consensus classification is available. Consider requesting a specialist opinion before altering any guidance.

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

Source

Classification

Review level

Last updated

Strength

ClinVar25 submissions on record.

Conflicting classifications

Conflicting submissions

31 Jan 2026

Limited

VCV000037640

Population frequencyHighest reported allele frequency carried on the source record.

0.00023

NHLBI Exome Sequencing Project (ESP) Exome Variant Server

31 Jan 2026

Reference observation

LiteraturePublications linked to this variant record.

8 indexed publications

PubMed index

Latest 2024

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

21 Nov 2022

On record

Record

Age band

Test date

As reported

Current

Department

Clinical owner

Last contact

Review state

VP-10876

35-44

21 Nov 2022

VUS

Conflicting

Clinical Genetics

Dr. M. Suleiman

4y ago

Not reviewed