VP-R-2026-008

MYBPC3 c.26-2A>G

Hypertrophic cardiomyopathy

Needs reviewHigh

Your DNA didn’t change. Science did. AI assists. Clinicians decide.

Classification change

2022 · On file

Pathogenic

Reported 16 Aug 2022

Science evolves

Today · ClinVar

Uncertain significance

ClinVar last evaluated 13 Nov 2025 · Reviewed by expert panel

The DNA has not changed. Only the interpretation has.MYBPC3 c.26-2A>G · identical in both

Classification drift

Variant

Gene: MYBPC3
HGVS (coding): c.26-2A>G
Protein: Not applicable
ClinVar: VCV000042644
dbSNP: rs376395543
Panel: Inherited cardiac conditions panel
Molecular consequence: splice acceptor variant

How the interpretation changed

MYBPC3 c.26-2A>G. The DNA is unchanged. The evidence around it is not.

2022Genetic test performedFirst record on file carrying MYBPC3 c.26-2A>G.
2022Reported as pathogenicCanonical splice-site change reported as pathogenic; family cascade testing and cardiac surveillance initiated.
2023Further literature published1 indexed publication appeared after the original report.
2025Submissions accumulated36 independent submissions now contribute to the classification.
2025Classification now uncertain significanceLast evaluated 13 Nov 2025 · Reviewed by expert panel.
TodayVariantPulse identified the affected records2 historical records carry this variant and were flagged for clinical review.

Evidence summary draft

AI draft · clinician must review

Evidence summary

Decision support

Since the 2022 report, the consensus for MYBPC3 c.26-2A>G has moved from pathogenic to uncertain significance. That reading rests on 36 submissions at strong review confidence, reviewed by expert panel. That moves the variant out of the clinically actionable band, so surveillance or management started on the original interpretation may no longer be indicated. 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.

Patient impact

The changed variant and every historical record that carries it. Select a record to see its detail.

Synthetic demonstration data

Changed variant

MYBPC3

c.26-2A>G

PathogenicVUS

VP-10654

Not reviewed

45-54 · Cardiology

Synthetic ID: VP-10654
Test date: 16 Aug 2022
Original classification: Pathogenicreported 16 Aug 2022
Current evidence: Uncertain significanceClinVar, evaluated 13 Nov 2025
Clinical owner: Dr. P. Varga
Review status: Not reviewed

Open record

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
ClinVar36 submissions on record.	Uncertain significance	Reviewed by expert panel	13 Nov 2025	Strong3 of 4 review criteria met	VCV000042644
Population frequencyHighest reported allele frequency carried on the source record.	8.00e-5	NHLBI Exome Sequencing Project (ESP) Exome Variant Server	13 Nov 2025	Reference observation
LiteraturePublications linked to this variant record.	8 indexed publications	PubMed index	Latest 2023	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.	Pathogenic	Internal report	16 Aug 2022	On record

Cited publications

The penetrance of rare variants in cardiomyopathy-associated genes: A cross-sectional approach to estimating penetrance for secondary findings. · Am J Hum Genet 2023 · PMID 37652022
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
Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). · Genet Med 2021 · PMID 34211152
Chromosomal microarray analysis, including constitutional and neoplastic disease applications, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG). · Genet Med 2021 · PMID 34131312
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
Diagnostic power and clinical impact of exome sequencing in a cohort of 500 patients with rare diseases. · Am J Med Genet C Semin Med Genet 2020 · PMID 33258288
Spatial and Functional Distribution of MYBPC3 Pathogenic Variants and Clinical Outcomes in Patients With Hypertrophic Cardiomyopathy. · Circ Genom Precis Med 2020 · PMID 32841044
Secondary findings in inherited heart conditions: a genotype-first feasibility study to assess phenotype, behavioural and psychosocial outcomes. · Eur J Hum Genet 2020 · PMID 32686758

How VariantPulse reached this resultEight steps, each one inspectable

1Historical record retrievedMYBPC3 c.26-2A>G reported as Pathogenic on 2022-08-16.
2Variant normalisedResolved to ClinVar VCV000042644 (rs376395543) and keyed as MYBPC3:c.26-2A>G.
3Current evidence retrievedRead live from ClinVar: Uncertain significance, 36 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 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.

Review priority

A triage signal for the queue. Not a clinical risk score, and not a statement about any individual.

+45Moved out of the actionable bandPathogenic to Uncertain significance. Earlier guidance may no longer apply.
+102 records on fileHistorical results carrying this variant that a reviewer would reassess.
+10High review confidenceThe current classification carries expert-panel or guideline review.

Ordering score65

Case trail

Every review action on this case, with who took it and when.

No review actions on this case yet.

Recommendation

Reassess 2 records against the current interpretation and decide whether the reporting clinician should be notified. Final interpretation remains with the clinical team.

Review actions

Each action is recorded in the audit trail. None changes a classification or a diagnosis.

Assign reviewer

Clinician note

Decision

A decision needs a clinician note of at least 10 characters. It records the outcome of the review; it does not write to any patient record or issue a diagnosis.

Case detail

Case: VP-R-2026-008
Raised: 1m ago
Assigned: Unassigned
Evidence source: ClinVar · Evidence monitor live
Records impacted: 2

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

Affected records in full

Synthetic demonstration data

Record	Age band	Test date	As reported	Current	Department	Clinical owner	Last contact	Review state
VP-10654	45-54	16 Aug 2022	Pathogenic	VUS	Cardiology	Dr. P. Varga	2y ago	Not reviewed
VP-10691	18-24	29 Nov 2022	Pathogenic	VUS	Cardiology	Dr. P. Varga	2y ago	Not reviewed

Source

Classification

Review level

Last updated

Strength

ClinVar36 submissions on record.

Uncertain significance

Reviewed by expert panel

13 Nov 2025

Strong

VCV000042644

Population frequencyHighest reported allele frequency carried on the source record.

8.00e-5

NHLBI Exome Sequencing Project (ESP) Exome Variant Server

13 Nov 2025

Reference observation

LiteraturePublications linked to this variant record.

8 indexed publications

PubMed index

Latest 2023

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.

Pathogenic

Internal report

16 Aug 2022

On record

Record

Age band

Test date

As reported

Current

Department

Clinical owner

Last contact

Review state

VP-10654

45-54

16 Aug 2022

Pathogenic

VUS

Cardiology

Dr. P. Varga

2y ago

Not reviewed

VP-10691

18-24

29 Nov 2022

Pathogenic

VUS

Cardiology

Dr. P. Varga

2y ago

Not reviewed