Patient record

VP-10543

35-44 · Male · Persistently raised LDL cholesterol

HighClassification drift

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

2022 · On file

Uncertain significance

Reported 11 Oct 2022

Science evolves

Today · ClinVar

Likely pathogenic

ClinVar last evaluated 23 Feb 2024 · Reviewed by expert panel

Patient summary

Record: VP-10543
Age band: 35-44
Sex: Male
Test date: 11 Oct 2022
Reporting laboratory: Genomics Core Laboratory
Ordering department: Lipid Clinic
Clinical owner: Dr. H. Nassar
Last contact: 6 Feb 2024
Indication: Persistently raised LDL cholesterol

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

Historical finding

ClinVar

LDLRc.1381G>T (p.Gly461Cys)

Panel: Lipid disorders panel
Condition: Familial hypercholesterolaemia
ClinVar: VCV000183113
dbSNP: rs193922568
As reported: Uncertain significance
Reported on: 11 Oct 2022

Missense change in the EGF-precursor homology domain. Reported as uncertain; segregation data not available.

Current interpretation

Read from ClinVar at the last evidence sync.

Classification: Likely pathogenic
Consensus status: Reviewed by expert panel
Evidence confidence: Strong3 of 4 review criteria met
Last evaluated: 23 Feb 2024
Submissions: 10
Molecular consequence: missense variant
Variant type: single nucleotide variant
Location: chr19:11113557 (GRCh38)

Evidence summary

Decision support

Since the 2022 report, the consensus for LDLR c.1381G>T has moved from uncertain significance to likely pathogenic. That reading rests on 10 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. 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 retrievedLDLR c.1381G>T reported as Uncertain significance on 2022-10-11.
2Variant normalisedResolved to ClinVar VCV000183113 (rs193922568) and keyed as LDLR:c.1381G>T.
3Current evidence retrievedRead live from ClinVar: Likely pathogenic, 10 submissions, reviewed by expert panel.
4Classification difference detectedRecorded interpretation normalised to Uncertain significance. Current interpretation normalised to Likely pathogenic. The interpretation crossed into the clinically actionable band, so records carrying it may need review.
5Regional sources comparedRegional index asserts Likely 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

Likely pathogenic

reviewed by expert panel · Last evaluated 23 Feb 2024

Regional · Regional Evidence Index

Likely pathogenic

0 observations in 3,042 · updated 27 Jan 2026

Sources consistent

Both lanes fall in the same clinical band.

Both sources place this variant in the same band.

Global

Likely pathogenic

Submissions: 10
Review status: Reviewed by expert panel
Last evaluated: 23 Feb 2024
Reference frequency: 1.00e-5

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

Regional

Likely pathogenic

Observations: 0
Cohort size: 3,042
Last updated: 27 Jan 2026
Regional frequency: 0.00e+0

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. Consistent with the global expert-panel reading. The familial hypercholesterolaemia mutation spectrum in Arab countries differs from European cohorts, which is why regional follow-up of LDLR results matters.

Spectrum of mutations of familial hypercholesterolemia in the 22 Arab countries. · Atherosclerosis 2018 · PMID 30415195

How the interpretation changed

LDLR c.1381G>T. The DNA is unchanged. The evidence around it is not.

2022Genetic test performedFirst record on file carrying LDLR c.1381G>T.
2022Reported as uncertain significanceMissense change in the EGF-precursor homology domain. Reported as uncertain; segregation data not available.
2024Submissions accumulated10 independent submissions now contribute to the classification.
2024Classification now likely pathogenicLast evaluated 23 Feb 2024 · Reviewed by expert panel.
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.