Hereditary cancer panel

BRCA1 c.1140dup

p.Lys381fs · Hereditary breast and ovarian cancer

No material changeNo review requiredVCV000231732 rs876659327

Then and now

Current evidence agrees with the interpretation on record.

2022 · On file

Pathogenic

Reported 3 Oct 2022

No material change

Today · ClinVar

Pathogenic

ClinVar last evaluated 15 Dec 2017 · Reviewed by expert panel

The DNA has not changed. Only the interpretation has.BRCA1 c.1140dup (p.Lys381fs) · 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

Variant

BRCA1

c.1140dup

PathogenicPathogenic

VP-10849

Closed

45-54 · Clinical Genetics

Synthetic ID: VP-10849
Test date: 3 Oct 2022
Original classification: Pathogenicreported 3 Oct 2022
Current evidence: PathogenicClinVar, evaluated 15 Dec 2017
Clinical owner: Dr. L. Haddad
Review status: Closed

Open record

Evidence summary

Decision support

Current evidence for BRCA1 c.1140dup agrees with the pathogenic interpretation issued in 2022. The classification was last evaluated on 15 Dec 2017 and carries 12 submissions.

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
ClinVar12 submissions on record.	Pathogenic	Reviewed by expert panel	15 Dec 2017	Strong3 of 4 review criteria met	VCV000231732
Population frequencyHighest reported allele frequency carried on the source record.	Not reported	No frequency data	15 Dec 2017	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	Pathogenic	0 regional observations	25 Sept 2026	Cohort 3,042
This institutionThe interpretation issued to the patient at the time of testing.	Pathogenic	Internal report	3 Oct 2022	On record

Cited publications

ATM-Related Cancer Predisposition. · University of Washington, Seattle 1993 · PMID 42258614
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
Assessing frequency and clinical outcomes of BRCA mutated ovarian cancer in Saudi women. · BMC Cancer 2022 · PMID 34980015
Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021. · Ann Oncol 2021 · PMID 34242744
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
Risk assessment and genetic counseling for hereditary breast and ovarian cancer syndromes-Practice resource of the National Society of Genetic Counselors. · J Genet Couns 2021 · PMID 33410258
Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA1/2-Related Cancer in Women: A Systematic Review for the U.S. Preventive Services Task Force · Agency for Healthcare Research and Quality (US) 2019 · PMID 31479213
Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: US Preventive Services Task Force Recommendation Statement. · JAMA 2019 · PMID 31429903

Global and regional evidence

Sources agree

Global · ClinVar

Pathogenic

reviewed by expert panel · Last evaluated 15 Dec 2017

Regional · Regional Evidence Index

Pathogenic

0 observations in 3,042 · updated 25 Sept 2026

Sources consistent

Both lanes fall in the same clinical band.

Both sources place this variant in the same band.

Global

Pathogenic

Submissions: 12
Review status: Reviewed by expert panel
Last evaluated: 15 Dec 2017
Reference frequency: Not reported

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

Regional

Pathogenic

Observations: 0
Cohort size: 3,042
Last updated: 25 Sept 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. CTGA records this frameshift in a UAE family (Rawashdeh et al. 2024) and a Yemeni patient (Al-Ali et al. 2023). Regional and global readings agree: pathogenic. Included as a control, so the system shows it does not raise an alert when nothing has changed.

How the interpretation changed

BRCA1 c.1140dup. The DNA is unchanged. The evidence around it is not.

2022Genetic test performedFirst record on file carrying BRCA1 c.1140dup.
2022Reported as pathogenicFrameshift change reported as pathogenic by expert-panel criteria. Surveillance and cascade testing offered.
2017Submissions accumulated12 independent submissions now contribute to the classification.
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.1140dup reported as Pathogenic on 2022-10-03.
2Variant normalisedResolved to ClinVar VCV000231732 (rs876659327) and keyed as BRCA1:c.1140dup.
3Current evidence retrievedRead live from ClinVar: Pathogenic, 12 submissions, reviewed by expert panel.
4Classification difference detectedRecorded interpretation normalised to Pathogenic. Current interpretation normalised to Pathogenic. Codes are identical, so no reclassification has occurred.
5Regional sources comparedRegional index asserts Pathogenic, consistent with the global reading.
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.

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-10849	45-54	3 Oct 2022	Pathogenic	Pathogenic	Clinical Genetics	Dr. L. Haddad	2y ago	Closed

Recommendation

No action required. Current evidence agrees with the interpretation on record.

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

Source

Classification

Review level

Last updated

Strength

ClinVar12 submissions on record.

Pathogenic

Reviewed by expert panel

15 Dec 2017

Strong

VCV000231732

Population frequencyHighest reported allele frequency carried on the source record.

Not reported

No frequency data

15 Dec 2017

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

Pathogenic

0 regional observations

25 Sept 2026

Cohort 3,042

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

Pathogenic

Internal report

3 Oct 2022

On record

Record

Age band

Test date

As reported

Current

Department

Clinical owner

Last contact

Review state

VP-10849

45-54

3 Oct 2022

Pathogenic

Clinical Genetics

Dr. L. Haddad

2y ago

Closed