Haemoglobinopathy panel

HBB c.380T>G

p.Val127Gly · Beta-thalassaemia / haemoglobinopathy

Regional conflictHighVP-R-2026-002VCV000015483 rs33925391

Then and now

Regional evidence reaches a different conclusion from the global consensus.

2023 · On file

Pathogenic

Reported 30 Jan 2023

Science evolves

Today · ClinVar

Uncertain significance

ClinVar last evaluated 30 Apr 2026 · Reviewed by expert panel

The DNA has not changed. Only the interpretation has.HBB c.380T>G (p.Val127Gly) · 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

HBB

c.380T>G

PathogenicVUS

VP-10728

Not reviewed

25-34 · Haematology

Synthetic ID: VP-10728
Test date: 30 Jan 2023
Original classification: Pathogenicreported 30 Jan 2023
Current evidence: Uncertain significanceClinVar, evaluated 30 Apr 2026
Clinical owner: Dr. F. Al Mazrouei
Review status: Not reviewed

Open record

Evidence summary

Decision support

Global and regional evidence disagree on HBB c.380T>G. The global consensus is uncertain significance, drawn from 9 submissions. The regional index asserts pathogenic on 0 observations across a cohort of 2,884. One source places this variant in the clinically actionable band and the other does not, which is the form of disagreement most likely to change a care decision. 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.	Uncertain significance	Reviewed by expert panel	30 Apr 2026	Strong3 of 4 review criteria met	VCV000015483
Population frequencyHighest reported allele frequency carried on the source record.	Not reported	No frequency data	30 Apr 2026	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	12 May 2026	Cohort 2,884
This institutionThe interpretation issued to the patient at the time of testing.	Pathogenic	Internal report	30 Jan 2023	On record

Cited publications

Strong Positive Dichlorophenolindophenol Precipitation Suggests Hb Dhonburi (or Hb Neapolis) (HBB: c.380T>G) Inheritance in a Couple at Risk for Severe β-Thalassemia. · Hemoglobin 2022 · PMID 35543019
Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes. · PLoS Genet 2019 · PMID 31589614
Molecular characteristics of thalassemia and hemoglobin variants in prenatal diagnosis program in northern Thailand. · Int J Hematol 2019 · PMID 31240559
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. · Genet Med 2017 · PMID 28492532
Next-generation sequencing improves thalassemia carrier screening among premarital adults in a high prevalence population: the Dai nationality, China. · Genet Med 2017 · PMID 28125089
A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders. · Hum Mutat 2016 · PMID 26467025
EMQN Best Practice Guidelines for molecular and haematology methods for carrier identification and prenatal diagnosis of the haemoglobinopathies. · Eur J Hum Genet 2015 · PMID 25052315
Problems in determining thalassemia carrier status in a program for prevention and control of severe thalassemia syndromes: a lesson from Thailand. · Clin Chem Lab Med 2013 · PMID 23525874

Global and regional evidence

Regional conflict

Global · ClinVar

Uncertain significance

reviewed by expert panel · Last evaluated 30 Apr 2026

Regional · Regional Evidence Index

Pathogenic

0 observations in 2,884 · updated 12 May 2026

Human review required

VUS globally, Pathogenic regionally. A clinician weighs both; neither source is treated as correct.

One source places this variant in the clinically actionable band and the other does not.

Global

Uncertain significance

Submissions: 9
Review status: Reviewed by expert panel
Last evaluated: 30 Apr 2026
Reference frequency: Not reported

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

Regional

Pathogenic

Observations: 0
Cohort size: 2,884
Last updated: 12 May 2026
Regional frequency: 0.00e+0

Modelled regional aggregation maintained inside this workspace.

VariantPulse analysis

One source places this variant in the clinically actionable band and the other does not. Global submitters downgraded this change to uncertain significance in April 2026. The regional index still carries the earlier pathogenic reading from haemoglobinopathy work-ups. Beta-thalassaemia carrier status is common in the UAE and drives premarital and reproductive counselling, so a disagreement here has direct family-planning consequences and must be resolved by a clinician, not by the software.

VariantPulse recommends manual review due to conflicting interpretation across evidence sources. It does not rank one source above the other.

Molecular basis of β-thalassemia in the United Arab Emirates. · Hemoglobin 2011 · PMID 22074124
Middle Eastern Genetic Variation Improves Clinical Annotation of the Human Genome. · J Pers Med 2022 · PMID 35330423

How the interpretation changed

HBB c.380T>G. The DNA is unchanged. The evidence around it is not.

2023Genetic test performedFirst record on file carrying HBB c.380T>G.
2023Reported as pathogenicReported as pathogenic following abnormal haemoglobin studies. Carrier status communicated for reproductive planning.
2026Submissions accumulated9 independent submissions now contribute to the classification.
2026Classification now uncertain significanceLast evaluated 30 Apr 2026 · 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 retrievedHBB c.380T>G reported as Pathogenic on 2023-01-30.
2Variant normalisedResolved to ClinVar VCV000015483 (rs33925391) and keyed as HBB:c.380T>G.
3Current evidence retrievedRead live from ClinVar: Uncertain significance, 9 submissions, reviewed by expert panel.
4Classification difference detectedRecorded interpretation normalised to Pathogenic. Current interpretation normalised to Uncertain significance. The interpretation left the clinically actionable band, so earlier management guidance may no longer apply.
5Regional sources comparedRegional index asserts Pathogenic across 0 observations. One source places this variant in the clinically actionable band and the other does not.
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.

+45Moved out of the actionable bandPathogenic to Uncertain significance. Earlier guidance may no longer apply.
+30Regional evidence conflictsRegional and global sources reach different conclusions.
+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 score90

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-10728	25-34	30 Jan 2023	Pathogenic	VUS	Haematology	Dr. F. Al Mazrouei	4y ago	Not reviewed

Recommendation

Manual review recommended: global and regional sources disagree, and VariantPulse does not rank one above the other. A clinician should weigh both against the patient context.

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

Source

Classification

Review level

Last updated

Strength

ClinVar9 submissions on record.

Uncertain significance

Reviewed by expert panel

30 Apr 2026

Strong

VCV000015483

Population frequencyHighest reported allele frequency carried on the source record.

Not reported

No frequency data

30 Apr 2026

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

12 May 2026

Cohort 2,884

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

Pathogenic

Internal report

30 Jan 2023

On record

Record

Age band

Test date

As reported

Current

Department

Clinical owner

Last contact

Review state

VP-10728

25-34

30 Jan 2023

Pathogenic

VUS

Haematology

Dr. F. Al Mazrouei

4y ago

Not reviewed