Patient record

VP-10122

45-54 · Male · Persistently raised LDL cholesterol

MediumRegional conflict

Regional evidence reaches a different conclusion from the global consensus.

Then2021

Uncertain significance

As reported

Science
changed

Now2022

Likely benign

Reviewed by expert panel

Patient summary

Record: VP-10122
Age band: 45-54
Sex: Male
Test date: 9 Aug 2021
Reporting laboratory: Genomics Core Laboratory
Ordering department: Lipid Clinic
Clinical owner: Dr. H. Nassar
Last contact: 21 May 2024
Indication: Persistently raised LDL cholesterol

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

Historical finding

ClinVar

LDLRc.1706-10G>A

Panel: Lipid disorders panel
Condition: Familial hypercholesterolaemia
ClinVar: VCV000226368
dbSNP: rs17248882
As reported: Uncertain significance
Reported on: 9 Aug 2021

Intronic change near the splice acceptor. Splicing impact undetermined at the time of reporting.

Current interpretation

Read from ClinVar at the last evidence sync.

Classification: Likely benign
Consensus status: Reviewed by expert panel
Evidence confidence: Strong3 of 4 review criteria met
Last evaluated: 16 Mar 2022
Submissions: 32
Molecular consequence: intron variant
Variant type: single nucleotide variant
Location: chr19:11116849 (GRCh38)

Evidence summary

Decision support

Global and regional evidence disagree on LDLR c.1706-10G>A. The global consensus is likely benign, drawn from 32 submissions. The regional index asserts likely pathogenic on 14 observations across a cohort of 6,850. 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 retrievedLDLR c.1706-10G>A reported as Uncertain significance on 2021-08-09.
2Variant normalisedResolved to ClinVar VCV000226368 (rs17248882) and keyed as LDLR:c.1706-10G>A.
3Current evidence retrievedRead live from ClinVar: Likely benign, 32 submissions, reviewed by expert panel.
4Classification difference detectedRecorded interpretation normalised to Uncertain significance. Current interpretation normalised to Likely benign. Evidence moved toward a benign interpretation.
5Regional sources comparedRegional index asserts Likely pathogenic across 14 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

Likely benign

Submissions: 32
Review status: Reviewed by expert panel
Last evaluated: 16 Mar 2022
Reference frequency: 2.53e-3

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

Regional

Likely pathogenic

Observations: 14
Cohort size: 6,850
Last updated: 11 Feb 2026
Regional frequency: 2.10e-3

Modelled regional aggregation maintained inside this workspace.

VariantPulse analysis

One source places this variant in the clinically actionable band and the other does not. Enriched in regional familial hypercholesterolaemia cohorts relative to the global reference set, with a splice-impact signal reported in affected families. The mutation spectrum of familial hypercholesterolaemia across Arab countries is documented as distinct from European cohorts, so a benign reading derived largely from European data does not settle the question here.

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

Spectrum of mutations of familial hypercholesterolemia in the 22 Arab countries. — Atherosclerosis 2018 · PMID 30415195
The Spectrum of Familial Hypercholesterolemia (FH) in Saudi Arabia: Prime Time for Patient FH Registry. — Open Cardiovasc Med J 2017 · PMID 28868092

How the interpretation changed

LDLR c.1706-10G>A — the DNA is unchanged. The evidence around it is not.

2021Genetic test performedFirst record on file carrying LDLR c.1706-10G>A.
2021Reported as uncertain significanceIntronic change near the splice acceptor. Splicing impact undetermined at the time of reporting.
2022Further literature published2 indexed publications appeared after the original report.
2022Submissions accumulated32 independent submissions now contribute to the classification.
2022Classification now likely benignLast evaluated 16 Mar 2022 · 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.