Evidence explorer

Evidence

Every source that contributes to an interpretation, shown separately. VariantPulse does not collapse them into a single verdict.

Reading live from ClinVarChecked just now12 variants on the monitored panelClinVar

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BRCA1 c.5522G>T

Hereditary breast and ovarian cancer · Hereditary cancer panel

Likely pathogenic

Last evaluated 6 Nov 2025

Evidence summary

Decision support

Since the 2023 report, the consensus for BRCA1 c.5522G>T has moved from uncertain significance to likely pathogenic. That reading rests on 3 submissions at moderate review confidence — multiple submitters, no conflicts. 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.

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
ClinVar3 submissions on record.	Likely pathogenic	Multiple submitters, no conflicts	6 Nov 2025	Moderate2 of 4 review criteria met	VCV000869004
Population frequencyHighest reported allele frequency carried on the source record.	Not reported	No frequency data	6 Nov 2025	Reference observation
LiteraturePublications linked to this variant record.	8 indexed publications	PubMed index	Latest 2021	Supporting context
Regional Evidence IndexModelled regional aggregation maintained inside this workspace	Pathogenic	3 regional observations	4 Mar 2026	Cohort 5,400
This institutionThe interpretation issued to the patient at the time of testing.	Uncertain significance	Internal report	18 Apr 2023	On record

Cited publications

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
Multigene panel testing for hereditary breast and ovarian cancer in the province of Ontario. — J Cancer Res Clin Oncol 2021 · PMID 32885271
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
Accurate classification of BRCA1 variants with saturation genome editing. — Nature 2018 · PMID 30209399
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
Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional Version. — National Cancer Institute (US) 2002 · PMID 26389258

Global and regional evidence

Sources agree

Global

Likely pathogenic

Submissions: 3
Review status: Multiple submitters, no conflicts
Last evaluated: 6 Nov 2025
Reference frequency: Not reported

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

Regional

Pathogenic

Observations: 3
Cohort size: 5,400
Last updated: 4 Mar 2026
Regional frequency: 2.80e-4

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. Regional observations are limited but fall in the same clinical band as the global consensus. No divergence to resolve.

How VariantPulse reached this resultEight steps, each one inspectable

1Historical record retrievedBRCA1 c.5522G>T reported as Uncertain significance on 2023-04-18.
2Variant normalisedResolved to ClinVar VCV000869004 (rs80357368) and keyed as BRCA1:c.5522G>T.
3Current evidence retrievedRead live from ClinVar: Likely pathogenic, 3 submissions, criteria provided, multiple submitters, no conflicts.
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 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.

Source

Classification

Review level

Last updated

Strength

ClinVar3 submissions on record.

Likely pathogenic

Multiple submitters, no conflicts

6 Nov 2025

Moderate

VCV000869004

Population frequencyHighest reported allele frequency carried on the source record.

Not reported

No frequency data

6 Nov 2025

Reference observation

LiteraturePublications linked to this variant record.

8 indexed publications

PubMed index

Latest 2021

Supporting context

Regional Evidence IndexModelled regional aggregation maintained inside this workspace

Pathogenic

3 regional observations

4 Mar 2026

Cohort 5,400

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

Uncertain significance

Internal report

18 Apr 2023

On record