Lipid disorders panel

LDLR c.2479G>A

p.Val827Ile · Familial hypercholesterolaemia

No material changeNo review requiredVCV000036462 rs137853964

Then and now

Current evidence agrees with the interpretation on record.

2022 · On file

Uncertain significance

Reported 4 Jul 2022

No material change

Today · ClinVar

Uncertain significance

ClinVar last evaluated 22 Jun 2021 · Reviewed by expert panel

The DNA has not changed. Only the interpretation has.LDLR c.2479G>A (p.Val827Ile) · 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

Variant

LDLR

c.2479G>A

VUSVUS

VP-10913

Reviewed

45-54 · Lipid Clinic

Synthetic ID: VP-10913
Test date: 4 Jul 2022
Original classification: Uncertain significancereported 4 Jul 2022
Current evidence: Uncertain significanceClinVar, evaluated 22 Jun 2021
Clinical owner: Dr. H. Nassar
Review status: Reviewed

Open record

Evidence summary

Decision support

Current evidence for LDLR c.2479G>A agrees with the uncertain significance interpretation issued in 2022. The classification was last evaluated on 22 Jun 2021 and carries 39 submissions.

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
ClinVar39 submissions on record.	Uncertain significance	Reviewed by expert panel	22 Jun 2021	Strong3 of 4 review criteria met	VCV000036462
Population frequencyHighest reported allele frequency carried on the source record.	0.00077	NHLBI Exome Sequencing Project (ESP) Exome Variant Server	22 Jun 2021	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	No regional record	Not held	-	-
This institutionThe interpretation issued to the patient at the time of testing.	Uncertain significance	Internal report	4 Jul 2022	On record

Cited publications

ACMG SF v3.1 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG). · Genet Med 2022 · PMID 35802134
Whole-exome sequencing reveals damaging gene variants associated with hypoalphalipoproteinemia. · J Lipid Res 2022 · PMID 35460704
Diagnosis of familial hypercholesterolemia in a large cohort of Italian genotyped hypercholesterolemic patients. · Atherosclerosis 2022 · PMID 35339733
ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). · Genet Med 2021 · PMID 34012068
Comparison of the mutation spectrum and association with pre and post treatment lipid measures of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries. · Atherosclerosis 2021 · PMID 33508743
The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia. · Genes (Basel) 2021 · PMID 33418990
Combined hyperlipidemia is genetically similar to isolated hypertriglyceridemia. · J Clin Lipidol 2021 · PMID 33303402
Polygenic Contribution to Low-Density Lipoprotein Cholesterol Levels and Cardiovascular Risk in Monogenic Familial Hypercholesterolemia. · Circ Genom Precis Med 2020 · PMID 33079599

How the interpretation changed

LDLR c.2479G>A. The DNA is unchanged. The evidence around it is not.

2022Genetic test performedFirst record on file carrying LDLR c.2479G>A.
2022Reported as uncertain significanceReported as uncertain significance by expert-panel criteria.
2021Submissions accumulated39 independent submissions now contribute to the classification.
TodayVariantPulse identified the affected records2 historical records carry this variant and were flagged for clinical review.

How VariantPulse reached this resultEight steps, each one inspectable

1Historical record retrievedLDLR c.2479G>A reported as Uncertain significance on 2022-07-04.
2Variant normalisedResolved to ClinVar VCV000036462 (rs137853964) and keyed as LDLR:c.2479G>A.
3Current evidence retrievedRead live from ClinVar: Uncertain significance, 39 submissions, reviewed by expert panel.
4Classification difference detectedRecorded interpretation normalised to Uncertain significance. Current interpretation normalised to Uncertain significance. Codes are identical, so no reclassification has occurred.
5Regional sources comparedNo regional evidence is held for this variant.
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.

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-10913	45-54	4 Jul 2022	VUS	VUS	Lipid Clinic	Dr. H. Nassar	3y ago	Reviewed
VP-10950	35-44	13 Feb 2023	VUS	VUS	Lipid Clinic	Dr. H. Nassar	3y ago	Reviewed

Recommendation

No action required. Current evidence agrees with the interpretation on record.

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

Source

Classification

Review level

Last updated

Strength

ClinVar39 submissions on record.

Uncertain significance

Reviewed by expert panel

22 Jun 2021

Strong

VCV000036462

Population frequencyHighest reported allele frequency carried on the source record.

0.00077

NHLBI Exome Sequencing Project (ESP) Exome Variant Server

22 Jun 2021

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

No regional record

Not held

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

Uncertain significance

Internal report

4 Jul 2022

On record

Record

Age band

Test date

As reported

Current

Department

Clinical owner

Last contact

Review state

VP-10913

45-54

4 Jul 2022

VUS

Lipid Clinic

Dr. H. Nassar

3y ago

Reviewed

VP-10950

35-44

13 Feb 2023

VUS

Lipid Clinic

Dr. H. Nassar

3y ago

Reviewed