What does this genetic variant mean? See actual evidence and tool calls

What does a genetic variant evidence result actually contain?

These are selected fields from actual public MCP responses retrieved on 2026-09-11. They are dated examples, not a live result or an independent clinical assessment. One variant call already includes annotation, automated classification, ClinVar assertions, population evidence, predictors when available and source versions.

What is known about BRCA1 c.68_69del?

Exact input: NM_007294.4:c.68_69del. Resolved identity: GRCh38:chr17:43124027:ACT:A.

Resolved gene and consequence

BRCA1; frameshift_variant

Automated Folklore classification

P (Pathogenic)

ClinVar assertion

Pathogenic; reviewed_by_expert_panel; 3 review stars

gnomAD allele frequency

0.0001184799984912388

gnomAD allele count / number

191 / 1612084

Classifier version

3.39.1

ClinVar assertions and the automated Folklore class are separate results. In this example, predictors, SpliceAI and conservation returned no_record; that is not evidence that the variant is benign. Consult the linked source versions when interpreting population values.

Which diseases are associated with FBN1?

A separate get_gene_disease_associations call with gene FBN1 returned the following 3 assertions. These describe gene–disease validity, not the pathogenicity of a particular variant. Disputed assessments are preserved.

• Marfan syndrome

  MONDO:0007947 · Definitive · inheritance: AD (autosomal dominant)

  General Gene Curation Expert Panel; assessment dated 2019-03-04.

• Shprintzen-Goldberg syndrome

  MONDO:0008426 · Disputed · inheritance: AD (autosomal dominant)

  Intellectual Disability and Autism Gene Curation Expert Panel; assessment dated 2021-12-01.

• familial thoracic aortic aneurysm and aortic dissection

  MONDO:0019625 · Definitive · inheritance: AD (autosomal dominant)

  Heritable Thoracic Aortic Aneurysm and Dissection Gene Curation Expert Panel; assessment dated 2017-01-23.

Source: ClinGen Gene-Disease Validity, clingen_gdv_2026-03-16.csv (ClinGen GDV export, FILE CREATED 2026-03-16). Gene-Disease Validity classifications obtained from the Clinical Genome Resource (ClinGen). Source version identifies the local reference export; it is not a claim of current upstream freshness. Coverage is limited to this snapshot. No matching assertion does not establish that a relationship is absent.

{
  "name": "get_gene_disease_associations",
  "arguments": {
    "gene": "FBN1",
    "limit": 5,
    "offset": 0
  }
}

Observed public results: 10 September 2026

These publisher-run snapshots preserve automated results, not clinical conclusions. Classifier 3.39.1 reported ClinVar 2026-01, gnomAD 4.1 and Ensembl VEP Release 113. Source assertions and automated classification remain separate. No record is different from evidence against pathogenicity.

{
  "name": "search_variant_evidence",
  "arguments": {
    "assembly": "GRCh38",
    "query": "NM_007294.4:c.68_69del"
  }
}

{
  "name": "search_variant_evidence",
  "arguments": {
    "assembly": "GRCh38",
    "query": "ENST00000226413.5:c.317A>G"
  }
}

{
  "name": "search_variant_evidence",
  "arguments": {
    "assembly": "GRCh38",
    "query": "GRCh38:chr17:43124027:ACT:A"
  }
}

{
  "name": "search_variant_evidence",
  "arguments": {
    "assembly": "GRCh38",
    "query": "chr17:43115777 A>G"
  }
}

{
  "name": "search_variant_evidence",
  "arguments": {
    "assembly": "GRCh38",
    "query": "chr17:43104953 G>C"
  }
}

{
  "name": "search_variant_evidence",
  "arguments": {
    "assembly": "GRCh38",
    "query": "rs80357914"
  }
}

{
  "name": "search_variant_evidence",
  "arguments": {
    "assembly": "GRCh38",
    "query": "NM_007294.3:c.68_69del"
  }
}

{
  "name": "search_variant_evidence",
  "arguments": {
    "assembly": "GRCh38",
    "query": "rs429358"
  }
}

Already have a ClinVar, Ensembl or publication record?

Use the exact public HGVS, rsID or verified GRCh38 allele from the record, preserving transcript versions. A gene name, phenotype or paper title alone is not a variant identity. Folklore resolves the supported allele and returns automated classification with available evidence and provenance.

Read submitted ClinVar assertions separately from the automated classification. When publications are requested, use the verified identity for variant literature search; a paper association does not establish pathogenicity. Missing evidence and ambiguous identities remain explicit.

Step-by-step agent flow

Call search_variant_evidence with GRCh38 and the public expression. Continue only if the result is resolved.

• Record normalized coordinates, alleles, gene, transcript and canonical key.
• Report the current automated classification and applied criteria.
• Group available evidence by source and preserve data versions.
• Use the canonical key for variant literature when requested.
• Inspect individual PMIDs only after they are returned by literature search.
• End with limitations and qualified professional review.

Identity checks with public examples

For a BRCA1 example, the verified public GRCh38 identity GRCh38:chr17:43124027:ACT:A resolves to BRCA1 ENST00000357654.9:c.68_69del. A separate non-BRCA example, ENST00000226413.5:c.317A>G, resolves to GNRHR. These examples show why a gene name or familiar short form must not replace exact allele and transcript verification.

• Preserve the transcript accession and version supplied by the user.
• If that transcript expression does not resolve, report the state instead of substituting a different transcript.
• Treat GRCh37 input as outside the current GRCh38 contract unless the user supplies a separately verified GRCh38 representation.
• Report structural variants and other unsupported variant types as unsupported.
• Read snapshot dates and versions; run a new query for the current classification.

Branch before you summarize

For an ambiguous result, show candidates and ask the user to choose. For not_found, invalid_request, unsupported or resolution_unavailable states, report the state directly. Never substitute a likely variant or a model-memory classification.