Hereditary cancer panel

PTEN c.149T>C

p.Ile50Thr · PTEN hamartoma tumour syndrome

Classification driftHighVP-R-2026-006VCV000492727 rs1554893824

Then and now

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

2022 · On file

Uncertain significance

Reported 5 Dec 2022

Science evolves

Today · ClinVar

Pathogenic

ClinVar last evaluated 9 Feb 2024 · Reviewed by expert panel

The DNA has not changed. Only the interpretation has.PTEN c.149T>C (p.Ile50Thr) · 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

PTEN

c.149T>C

VUSPathogenic

VP-10617

Not reviewed

5-11 · Paediatric Genetics

Synthetic ID: VP-10617
Test date: 5 Dec 2022
Original classification: Uncertain significancereported 5 Dec 2022
Current evidence: PathogenicClinVar, evaluated 9 Feb 2024
Clinical owner: Dr. S. Aziz
Review status: Not reviewed

Open record

Evidence summary

Decision support

Since the 2022 report, the consensus for PTEN c.149T>C has moved from uncertain significance to pathogenic. That reading rests on 9 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. 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
ClinVar9 submissions on record.	Pathogenic	Reviewed by expert panel	9 Feb 2024	Strong3 of 4 review criteria met	VCV000492727
Population frequencyHighest reported allele frequency carried on the source record.	0.00e+0	The Genome Aggregation Database (gnomAD), exomes	9 Feb 2024	Reference observation
LiteraturePublications linked to this variant record.	8 indexed publications	PubMed index	Latest 2026	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	5 Dec 2022	On record

Cited publications

Phenotypic manifestations and variant reclassification of germline PTEN variants: a nationwide Danish study. · J Med Genet 2026 · PMID 42716728
Investigation into the genetics of fetal congenital lymphatic anomalies. · Prenat Diagn 2023 · PMID 36959127
Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes. · Nat Genet 2022 · PMID 35982159
Gene-specific criteria for PTEN variant curation: Recommendations from the ClinGen PTEN Expert Panel. · Hum Mutat 2018 · PMID 30311380
Multiplex assessment of protein variant abundance by massively parallel sequencing. · Nat Genet 2018 · PMID 29785012
A Saturation Mutagenesis Approach to Understanding PTEN Lipid Phosphatase Activity and Genotype-Phenotype Relationships. · Am J Hum Genet 2018 · PMID 29706350
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

How the interpretation changed

PTEN c.149T>C. The DNA is unchanged. The evidence around it is not.

2022Genetic test performedFirst record on file carrying PTEN c.149T>C.
2022Reported as uncertain significanceMissense change reported by a single submitter as uncertain significance.
2023Further literature published2 indexed publications appeared after the original report.
2024Submissions accumulated9 independent submissions now contribute to the classification.
2024Classification now pathogenicLast evaluated 9 Feb 2024 · Reviewed by expert panel.
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 retrievedPTEN c.149T>C reported as Uncertain significance on 2022-12-05.
2Variant normalisedResolved to ClinVar VCV000492727 (rs1554893824) and keyed as PTEN:c.149T>C.
3Current evidence retrievedRead live from ClinVar: Pathogenic, 9 submissions, reviewed by expert panel.
4Classification difference detectedRecorded interpretation normalised to Uncertain significance. Current interpretation normalised to Pathogenic. The interpretation crossed into the clinically actionable band, so records carrying it may need review.
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.

+60Moved into the actionable bandUncertain significance to Pathogenic.
+51 record on fileHistorical results carrying this variant that a reviewer would reassess.
+10High review confidenceThe current classification carries expert-panel or guideline review.

Ordering score75

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-10617	5-11	5 Dec 2022	VUS	Pathogenic	Paediatric Genetics	Dr. S. Aziz	3y ago	Not reviewed

Recommendation

Reassess 1 record against the current interpretation and decide whether the reporting clinician should be notified. Final interpretation remains with the clinical team.

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

Source

Classification

Review level

Last updated

Strength

ClinVar9 submissions on record.

Pathogenic

Reviewed by expert panel

9 Feb 2024

Strong

VCV000492727

Population frequencyHighest reported allele frequency carried on the source record.

0.00e+0

The Genome Aggregation Database (gnomAD), exomes

9 Feb 2024

Reference observation

LiteraturePublications linked to this variant record.

8 indexed publications

PubMed index

Latest 2026

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

5 Dec 2022

On record

Record

Age band

Test date

As reported

Current

Department

Clinical owner

Last contact

Review state

VP-10617

5-11

5 Dec 2022

VUS

Pathogenic

Paediatric Genetics

Dr. S. Aziz

3y ago

Not reviewed