A 1-bp duplication in TGFB2 in three family members with a syndromic form of thoracic aortic aneurysm.
The main results reproduced: recomputed values matched the published ones within tolerance.
Every item that counted toward this verdict, and the exact part of the reproduction that produced it.
- ✓Same input data as the authors
- ✓Reported values were directly comparable
- ✓No relevant deviation in data/preprocessing
- ✓No authors-side cause for any deviation
- ✓Reported values are derivable from the shared data
- ✓Any deviation was negligible
- ✓The central claim held under reproduction
- ✓Overall, the reproduction was clean
- Every checked point held up.
A 0–100 reproducibility-quality score from the per-question grades, shown as a z-score: standard deviations above (+) or below (−) the mean of comparable assessments.
▸Reproduction agent’s raw note
Described well enough to reproduce the in-scope computational result EXACTLY. This is a clinical-genetics case report (Leutermann et al., EJHG 2014) whose only pipeline-/computation-derivable results are variant annotations. The reported consequence of TGFB2 c.1165dupA, p.Ser389Lysfs8, reproduces 1:1 two independent ways on RefSeq NM_001135599 (NP_001129071): (a) a deterministic CDS translation run as a «our HPC» SLURM job («job», node n094; ref codon389 AGC=Ser -> AAG=Lys, frameshift, stop at +8; mutant tail KQGPELI; match=true), and (b) the authoritative VariantValidator engine (NP_001129071.1:p.(Ser389LysfsTer8)). The 'exon 7' location also reproduces exactly (VariantValidator exon mapping). The NMD-escape rationale behind the 'stable transcript' claim is computationally consistent (PTC in the terminal exon). KEY AUDIT NOTE: the reported value is transcript-specific -- it holds on the 442-aa isoform NM_001135599 but NOT on NM_003238 (414 aa), where the same cDNA event gives p.Thr389Asnfs*13; the abstract does not state which transcript was used. NO fabrication indicators: every in-scope value is fully reconstructible from public reference data and two independent engines agree with the paper. NOT attempted (wet-lab, no deposited data): the 88-individual Sanger cohort screen that discovered the variant, family segregation, and the functional/expression experiments -- this paper deposited no primary sequencing data or variant-database accession. Overall: in-scope computational claims reproduce exactly; the discovery itself is wet-lab and unreproducible from deposited data, hence status=partial.
These records describe the outcome of reproduction attempts carried out autonomously by brainbox using large language models (LLMs). They are not peer review, not an audit, and not a determination of error or misconduct by any author. A verdict reflects what one attempt could or could not reproduce — which may depend on data access, undocumented parameters, the computing environment, or the depth of effort — and not a judgement of the people who did the work. We can be wrong, and we correct mistakes quickly: every record carries a “report an error” button.
Assessment versions
Every reproduction run is kept as an immutable version — anchored to the data as it stood, with a tamper-evident chain hash. A rerun (e.g. after an author updates a deposit) adds a new version; the previous one stays on record.
-
v1 current initial assessment Score 83assessed: 2026-06-19 ⛓ 4dfa5ce00ffc
✎ I am an author of this paper
Updated or fixed a deposit, or is there an erratum? Ask us to re-run the metrics. We verify by email first; the new result is published as a new version with full history — nothing is overwritten.
Provenance — full disclosure
When this reproduction was carried out, which methodology version was used, and by whom — so the record can be audited and checked independently.
- Reproduced
- 2026-06-19
- Rubric version
- v1.0
- Assessed by
-
🤖 AI curator · v1.0 · run #1 2026-06-19no human curator yet
- Last updated
- 2026-08-05
Provisional, curator- or AI-assessed, and independently checkable. A reproduction outcome states what one attempt could reproduce — not a judgement of the authors.
Deep full-text extraction
Model: opusThe authors test whether heterozygous loss-of-function mutations in TGFB2 underlie syndromic thoracic aortic aneurysm and dissection (TAAD), hypothesizing that functional haploinsufficiency for TGF-β2 predisposes to thoracic aortic disease.
- ★ A novel heterozygous c.1165dupA mutation in exon 7 of TGFB2 (p.Ser389Lysfs*8) was identified in three members of one family with syndromic TAAD. finding
- ★ The 1-bp duplication causes a frameshift producing a stable transcript with a premature stop codon after seven TGF-β2-unrelated amino acids, yielding a likely non-functional protein. mechanism
- ★ Functional haploinsufficiency for TGF-β2 predisposes to thoracic aortic disease. mechanism
- ★ TGFB2 is a rarely mutated gene in patients with syndromic TAAD. finding
- ★ The clinical features of the TGFB2 mutation-positive individuals fit the Loeys–Dietz syndrome scheme rather than MFS-related disorders. finding
- TGFB2 sequencing of a cohort of 88 individuals with Marfan-like phenotype and/or TAAD lacking mutations in known thoracic aortic disease genes. method
| Assay | System | Perturbation | Readout | Platform |
|---|---|---|---|---|
| Sanger sequencing of TGFB2 gene | cohort of 88 individuals with Marfan-like phenotype and/or TAAD (human) | none | presence of TGFB2 sequence variants/mutations | — |
| transcript/mRNA stability analysis | patient-derived cells (human, TGFB2 c.1165dupA carriers) | heterozygous c.1165dupA frameshift mutation | transcript stability and premature stop codon | — |
- – Heterozygous c.1165dupA (p.Ser389Lysfs*8) identified in three family members (proband, brother, nephew) with aortic aneurysms, cervical arterial tortuosity and/or skeletal abnormalities and craniofacial dysmorphisms.
- – Frameshift leads to a stable transcript with a premature stop codon after seven TGF-β2-unrelated amino acids, predicting a non-functional protein.
- – Only one TGFB2 mutation was found among the 88-individual cohort, indicating TGFB2 is rarely mutated in syndromic TAAD.
- count 88 (individuals with Marfan-like phenotype and/or TAAD screened by TGFB2 sequencing)
- count three (family members carrying the c.1165dupA TGFB2 mutation)
- count 51-year-old male (index patient age)
Statistical methods review
Model: sonnetA neutral, descriptive read of the statistical approach — what was done, and (for shared learning, not as criticism) what could also have been done.
This short report describes a candidate-gene sequencing study: the TGFB2 gene was sequenced in a cohort of 88 individuals with a Marfan-like phenotype and/or thoracic aortic aneurysm/dissection who lacked mutations in known causal genes, identifying a novel heterozygous frameshift variant in three affected members of one family. The available text presents this as a descriptive genetic/clinical case-series finding rather than a hypothesis-testing study with quantitative statistical comparisons, and no formal statistical tests, sample-size justification, or software are described in the provided text.
-
The study screened a cohort of 88 individuals by sequencing and reports findings as a descriptive case series (a novel variant found in three related affected individuals) without apparent formal statistical hypothesis testing.↳ Could also: A case-control or population-frequency comparison approach (e.g., comparing variant frequency in the cohort against a reference population database such as gnomAD/ExAC using a Fisher's exact test) could also be used. — This would provide a formal statistical estimate of how unlikely the variant's presence/frequency is under a null model, complementing segregation and functional evidence for pathogenicity.
-
Evidence for pathogenicity is built from segregation of the variant with disease in three family members and reasoning about predicted protein truncation/loss of function.↳ Could also: A formal LOD score or segregation-based likelihood analysis could also be used when pedigree size allows. — Quantifying the statistical support for co-segregation (even informally, given the small pedigree) can complement qualitative segregation arguments used to support causality.
-
The functional consequence of the frameshift variant (premature stop codon, likely non-functional protein) is inferred from the predicted transcript/protein change and comparison with prior literature on similar loss-of-function TGFB2 mutations.↳ Could also: Direct functional or expression assays (e.g., quantifying mRNA levels via qPCR to assess nonsense-mediated decay, or protein-level assays of TGF-β2 activity) could also be used. — Such assays would provide direct quantitative, statistically testable data (e.g., comparing expression levels between carriers and non-carriers) on haploinsufficiency, complementing the sequence-based prediction.
-
In silico or literature-based reasoning is used to support that the truncated protein is 'unlikely functional.'↳ Could also: Formal variant classification frameworks (e.g., ACMG/AMP criteria with computed PP/PVS evidence codes) could also be applied and reported. — This offers a standardized, reproducible framework for communicating the strength of evidence for pathogenicity alongside the descriptive reasoning presented.
What was reproduced
The exact results taken into scope, with each reported value next to the value our attempt produced.
Scope — PMID 24193348
Title: A 1-bp duplication in TGFB2 in three family members with a syndromic form of thoracic aortic aneurysm. Authors: Leutermann R, Sheikhzadeh S, Brockstädt L, Rybczynski M, van Rahden V, Kutsche K, von Kodolitsch Y, Rosenberger G. Journal: European Journal of Human Genetics (2014); Epub 2013-11-06. DOI 10.1038/ejhg.2013.252. PMCID PMC4060107.
Nature of the paper
A clinical/molecular-genetics case report. The authors screened the TGFB2 gene (targeted, Sanger-type gene sequencing) in a cohort of 88 individuals with thoracic aortic aneurysm/dissection (TAAD) and identified a novel heterozygous frameshift duplication c.1165dupA in exon 7 of TGFB2, predicted p.Ser389Lysfs*8, segregating in three members of one family. They argue for haploinsufficiency of TGF-β2, supported by transcript-/protein-level wet-lab experiments.
In scope (pipeline-/computation-derived, reproduced)
The only deterministic, computationally reproducible results are the variant annotations the paper reports — these are derivable from a reference transcript with a standard HGVS/translation engine (a third-party tool applied to the paper's own claim, explicitly endorsed by the brief, rule P16):
| # | Reported result | Paper location | Pipeline used to reproduce |
|---|---|---|---|
| C1 | Protein consequence p.Ser389Lysfs*8 | Title + Abstract | deterministic CDS translation (SLURM job on «our HPC») and VariantValidator REST (NP_001129071.1) |
| C2 | Variant lies in exon 7 of TGFB2 | Abstract | VariantValidator exon mapping (NM_001135599 / NG_027721.1) |
| C3 | Frameshift → premature stop → stable transcript (i.e. NMD-escape rationale) | Abstract | exon-structure analysis: PTC maps to the terminal exon → predicted to escape NMD (computational support for the wet-lab finding) |
Bonus auditable genomic descriptors (not numbers the paper printed, but verifiable):
GRCh37 NC_000001.10:g.218610833dup, GRCh38 NC_000001.11:g.218437491dup.
Out of scope (wet-lab / no deposited data — NOT attempted)
- Cohort screening of 88 TAAD individuals by Sanger sequencing — the discovery itself. No raw sequencing data (FASTQ/BAM/VCF) or accession was deposited; not reproducible.
- Segregation in the family (3 carriers) — wet-lab Sanger genotyping, no data deposited.
- Transcript stability / haploinsufficiency experiments (RT-PCR, expression assays, TGF-β signalling read-outs) — wet-lab functional work.
- SMART protein-domain annotation — a web tool; the abstract gives no specific SMART output number to compare against, so nothing quantitative to grade.
Key audit finding (transcript ambiguity)
The reported p.Ser389Lysfs*8 is transcript-specific. It reproduces exactly only
on the longer TGFB2 isoform NM_001135599 (NP_001129071, 442-aa precursor; codon 389 =
AGC = Ser). On the other common RefSeq NM_003238 (NP_003229, 414-aa precursor; codon
389 = ACC = Thr) the identical cDNA event yields p.Thr389Asnfs*13 instead. The paper's
value is correct for the transcript they (implicitly) used; the transcript ID is not stated
in the abstract — flagged for the human reviewer, not a discrepancy in the paper's result.
Assessments & scoring basis
Each contributor’s verdict, the per-question basis, and the auditable, itemised worksheet behind it.
An automated assessment. It can flag an open question for review but can never, on its own, record a discrepancy verdict (C5) against a paper.
Every item that counted toward this verdict, and the exact part of the reproduction that produced it.
Automated reproduction checks whether a published result can be regenerated from the paper’s described methods and shared data. When something does not reproduce, that is not a claim of error or misconduct — most often it reflects under-described methods, software or environment differences, or gaps in data access, and some of the pre-print papers in the queue may carry issues their authors had no part in. The goal is shared awareness that rigorous, fully-described methods help everyone — never a judgement of any author.
Are you an author? We would genuinely like to hear from you — to clarify the record, add data or code, re-run the pipeline after an accession update, and publish your response right next to the assessment. Everything here is open and auditable.
🚩 Report an error in this record
Spotted something wrong — a verdict you’d contest, a data or value error, or a private detail that slipped through? Tell us, with a short justification. Authors and readers are equally welcome to write in; we review every report.
Prefer email, or the form below not working? Contact us at support@doesitreproduce.com.
Reproduction footprint
claude-opus-4-8Measured resources invested to assess this paper — sanitised (machine class only, no job ids/paths). Compute = HPC accounting (SLURM); tokens = the AI agent's session.