Gastrointestinal cancer panel

APC c.4399C>T

p.Pro1467Ser · Familial adenomatous polyposis

No material changeNo review requiredVCV000411419 rs749142480

Then and now

Current evidence agrees with the interpretation on record.

Then2022

Benign

As reported

Science
changed

Now2023

Benign

Reviewed by expert panel

Evidence summary

Decision support

Current evidence for APC c.4399C>T agrees with the benign interpretation issued in 2022. The classification was last evaluated on 26 Feb 2023 and carries 11 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
ClinVar11 submissions on record.	Benign	Reviewed by expert panel	26 Feb 2023	Strong3 of 4 review criteria met	VCV000411419
Population frequencyHighest reported allele frequency carried on the source record.	5.00e-5	The Genome Aggregation Database (gnomAD), exomes	26 Feb 2023	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	Benign	87 regional observations	30 Jan 2026	Cohort 5,400
This institutionThe interpretation issued to the patient at the time of testing.	Benign	Internal report	5 Sept 2022	On record

Cited publications

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
European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender. — Br J Surg 2021 · PMID 34043773
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
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
A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders. — Hum Mutat 2016 · PMID 26467025
Genetics of Colorectal Cancer (PDQ®): Health Professional Version. — National Cancer Institute (US) 2002 · PMID 26389505
Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional Version. — National Cancer Institute (US) 2002 · PMID 26389258

Global and regional evidence

Sources agree

Global

Benign

Submissions: 11
Review status: Reviewed by expert panel
Last evaluated: 26 Feb 2023
Reference frequency: 5.00e-5

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

Regional

Benign

Observations: 87
Cohort size: 5,400
Last updated: 30 Jan 2026
Regional frequency: 1.61e-2

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. Common in both regional and global cohorts. Benign in both readings.

How the interpretation changed

APC c.4399C>T — the DNA is unchanged. The evidence around it is not.

2022Genetic test performedFirst record on file carrying APC c.4399C>T.
2022Reported as benignObserved at appreciable population frequency. Reported as benign and excluded from the clinical summary.
2023Submissions accumulated11 independent submissions now contribute to the classification.
TodayVariantPulse identified the affected records4 historical records carry this variant and were flagged for clinical review.

How VariantPulse reached this resultEight steps, each one inspectable

1Historical record retrievedAPC c.4399C>T reported as Benign on 2022-09-05.
2Variant normalisedResolved to ClinVar VCV000411419 (rs749142480) and keyed as APC:c.4399C>T.
3Current evidence retrievedRead live from ClinVar: Benign, 11 submissions, reviewed by expert panel.
4Classification difference detectedRecorded interpretation normalised to Benign. Current interpretation normalised to Benign. Codes are identical, so no reclassification has occurred.
5Regional sources comparedRegional index asserts Benign, 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.

Records carrying this variant

Historical findings in the connected record system that reference this variant.

Record	Age band	Test date	As reported	Current	Department	Clinical owner	Last contact	Review state
VP-10611	45-54	5 Sept 2022	Benign	Benign	Gastroenterology	Dr. M. Suleiman	4y ago	Closed
VP-10639	35-44	17 Oct 2022	Benign	Benign	Gastroenterology	Dr. M. Suleiman	4y ago	Closed
VP-10684	55-64	24 Jan 2023	Benign	Benign	Gastroenterology	Dr. H. Nassar	4y ago	Closed
VP-10742	25-34	6 Mar 2023	Benign	Benign	Clinical Genetics	Dr. L. Haddad	4y 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

ClinVar11 submissions on record.

Benign

Reviewed by expert panel

26 Feb 2023

Strong

VCV000411419

Population frequencyHighest reported allele frequency carried on the source record.

5.00e-5

The Genome Aggregation Database (gnomAD), exomes

26 Feb 2023

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

Benign

87 regional observations

30 Jan 2026

Cohort 5,400

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

Benign

Internal report

5 Sept 2022

On record

Record

Age band

Test date

As reported

Current

Department

Clinical owner

Last contact

Review state

VP-10611

45-54

5 Sept 2022

Benign

Gastroenterology

Dr. M. Suleiman

4y ago

Closed

VP-10639

35-44

17 Oct 2022

Benign

Gastroenterology

Dr. M. Suleiman

4y ago

Closed

VP-10684

55-64

24 Jan 2023

Benign

Gastroenterology

Dr. H. Nassar

4y ago

Closed

VP-10742

25-34

6 Mar 2023

Benign

Clinical Genetics

Dr. L. Haddad

4y ago

Closed