Patient record

VP-10701

25-34 · Female · Premarital screening follow-up

HighClassification drift

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

2023 · On file

Conflicting classifications

Reported 14 Feb 2023

Science evolves

Today · ClinVar

Pathogenic

ClinVar last evaluated 6 Mar 2026 · Multiple submitters, no conflicts

Patient summary

Record: VP-10701
Age band: 25-34
Sex: Female
Test date: 14 Feb 2023
Reporting laboratory: Molecular Pathology Unit
Ordering department: Haematology
Clinical owner: Dr. F. Al Mazrouei
Last contact: 7 Mar 2023
Indication: Premarital screening follow-up

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

Historical finding

ClinVar

HBBc.364G>C (p.Glu122Gln)

Panel: Haemoglobinopathy panel
Condition: Haemoglobinopathy (Hb D-Punjab)
ClinVar: VCV000015152
dbSNP: rs33946267
As reported: Conflicting classifications
Reported on: 14 Feb 2023

Haemoglobin D-Punjab. Global submitters disagreed at the time of reporting, so the result was filed without a firm classification. CTGA already recorded it in UAE patients with sickle cell disease and beta-thalassaemia.

Current interpretation

Read from ClinVar at the last evidence sync.

Classification: Pathogenic
Consensus status: Multiple submitters, no conflicts
Evidence confidence: Moderate2 of 4 review criteria met
Last evaluated: 6 Mar 2026
Submissions: 23
Molecular consequence: missense variant
Variant type: single nucleotide variant
Location: chr11:5225678 (GRCh38)

Evidence summary

Decision support

Since the 2023 report, the consensus for HBB c.364G>C has moved from conflicting classifications to pathogenic. That reading rests on 23 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. 2 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.

How VariantPulse reached this resultEight steps, each one inspectable

1Historical record retrievedHBB c.364G>C reported as Conflicting classifications on 2023-02-14.
2Variant normalisedResolved to ClinVar VCV000015152 (rs33946267) and keyed as HBB:c.364G>C.
3Current evidence retrievedRead live from ClinVar: Pathogenic/Likely pathogenic, 23 submissions, criteria provided, multiple submitters, no conflicts.
4Classification difference detectedRecorded interpretation normalised to Conflicting classifications. Current interpretation normalised to 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; 2 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.

Global and regional evidence

Sources agree

Global · ClinVar

Pathogenic

criteria provided, multiple submitters, no conflicts · Last evaluated 6 Mar 2026

Regional · Regional Evidence Index

Pathogenic

11 observations in 3,031 · updated 25 Sept 2026

Sources consistent

Both lanes fall in the same clinical band.

Both sources place this variant in the same band.

Global

Pathogenic

Submissions: 23
Review status: Multiple submitters, no conflicts
Last evaluated: 6 Mar 2026
Reference frequency: 6.00e-4

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

Regional

Pathogenic

Observations: 11
Cohort size: 3,031
Last updated: 25 Sept 2026
Regional frequency: 1.81e-3

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. Haemoglobin D-Punjab. CTGA records it in UAE patients as likely pathogenic / pathogenic for sickle cell disease and beta-thalassaemia, and it is about four times more frequent in gnomAD's Middle Eastern group than globally. Global ClinVar submitters were still in conflict in January 2023 and only converged on pathogenic / likely pathogenic in March 2026: regional evidence was ahead of the global record.

Molecular basis of β-thalassemia in the United Arab Emirates. · Hemoglobin 2011 · PMID 22074124

How the interpretation changed

HBB c.364G>C. The DNA is unchanged. The evidence around it is not.

2023Genetic test performedFirst record on file carrying HBB c.364G>C.
2023Reported as conflicting classificationsHaemoglobin D-Punjab. Global submitters disagreed at the time of reporting, so the result was filed without a firm classification. CTGA already recorded it in UAE patients with sickle cell disease and beta-thalassaemia.
2026Submissions accumulated23 independent submissions now contribute to the classification.
2026Classification now pathogenicLast evaluated 6 Mar 2026 · Multiple submitters, no conflicts.
TodayVariantPulse identified the affected records2 historical records carry this variant and were flagged for clinical review.

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