Patient record

VP-10728

25-34 · Female · Premarital screening follow-up

HighRegional conflict

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

Patient summary

Record: VP-10728
Age band: 25-34
Sex: Female
Test date: 30 Jan 2023
Reporting laboratory: Molecular Pathology Unit
Ordering department: Haematology
Clinical owner: Dr. F. Al Mazrouei
Last contact: 22 Feb 2023
Indication: Premarital screening follow-up

Synthetic record. No identifiers in this workspace correspond to a real person.

Historical finding

ClinVar

HBBc.380T>G (p.Val127Gly)

Panel: Haemoglobinopathy panel
Condition: Beta-thalassaemia / haemoglobinopathy
ClinVar: VCV000015483
dbSNP: rs33925391
As reported: Pathogenic
Reported on: 30 Jan 2023

Reported as pathogenic following abnormal haemoglobin studies. Carrier status communicated for reproductive planning.

Current interpretation

Read from ClinVar at the last evidence sync.

Classification: Uncertain significance
Consensus status: Reviewed by expert panel
Evidence confidence: Strong3 of 4 review criteria met
Last evaluated: 30 Apr 2026
Submissions: 9
Molecular consequence: missense variant
Variant type: single nucleotide variant
Location: chr11:5225662 (GRCh38)

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.

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.

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.

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