/shaip/variantvalidator

Purpose

Full HGVS validation using the RefSeq transcript set.

Supports:

• cDNA HGVS
• Genomic HGVS
• Protein HGVS
• Intronic variants
• Allele expressions

This endpoint is intended for validation, correction, and interpretation of HGVS descriptions, including complex and uncertain cases.

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Method

POST

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Path

/shaip/variantvalidator

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Input

Parameter	Type	Required	Description
variant_description	string or array	Yes	HGVS, VCF or pseudo-VCF variant description(s).
genome_build	string	Yes	Reference genome build (GRCh37 or GRCh38).
select_transcripts	string or array	Yes	Transcript selection mode or transcript accession(s). See transcript_selection.md.
liftover_level	string or bool	No	Controls genomic liftover. True performs full liftover, primary excludes alternative scaffolds, and False disables liftover. Defaults to True.

---

Example

[
  {
    "variant_description": "NM_000546.6:c.215C>G",
    "genome_build": "GRCh38",
    "select_transcripts": "mane_select",
    "liftover_level": "True"
  }
]

---

Example Response

{
  "flag": "gene_variant",
  "NM_000546.6:c.215C>G": {
    "selected_assembly": "GRCh38",
    "submitted_variant": "NM_000546.6:c.215C>G",
    "gene_symbol": "TP53",
    "gene_ids": {
      "hgnc_id": "HGNC:11998",
      "entrez_gene_id": "7157",
      "ensembl_gene_id": "ENSG00000141510",
      "ucsc_id": "uc060aur.1",
      "omim_id": [
        "191170"
      ],
      "ccds_ids": [
        "CCDS11118",
        "CCDS45605",
        "CCDS45606",
        "CCDS73969",
        "CCDS73970",
        "CCDS73971",
        "CCDS73964",
        "CCDS73967",
        "CCDS73963",
        "CCDS73968",
        "CCDS73965",
        "CCDS73966"
      ]
    },
    "annotations": {
      "db_xref": {
        "CCDS": "CCDS11118.1",
        "select": "MANE",
        "ncbigene": "7157",
        "ensemblgene": null,
        "hgnc": "HGNC:11998"
      },
      "chromosome": "17",
      "map": "17p13.1",
      "note": "tumor protein p53",
      "variant": "1",
      "refseq_select": true,
      "mane_select": true,
      "ensembl_select": false,
      "mane_plus_clinical": false
    },
    "transcript_description": "Homo sapiens tumor protein p53 (TP53), transcript variant 1, mRNA",
    "hgvs_transcript_variant": "NM_000546.6:c.215C>G",
    "rna_variant_descriptions": null,
    "genome_context_intronic_sequence": "",
    "refseqgene_context_intronic_sequence": "",
    "hgvs_refseqgene_variant": "",
    "hgvs_predicted_protein_consequence": {
      "tlr": "NP_000537.3:p.(Pro72Arg)",
      "slr": "NP_000537.3:p.(P72R)",
      "lrg_tlr": "LRG_321p1:p.(Pro72Arg)",
      "lrg_slr": "LRG_321p1:p.(P72R)"
    },
    "validation_warnings": [],
    "lovd_messages": null,
    "lovd_corrections": null,
    "hgvs_lrg_transcript_variant": "",
    "hgvs_lrg_variant": "",
    "alt_genomic_loci": [],
    "primary_assembly_loci": {
      "grch37": {
        "hgvs_genomic_description": "NC_000017.10:g.7579472G>C",
        "vcf": {
          "chr": "17",
          "pos": "7579472",
          "ref": "G",
          "alt": "C"
        }
      },
      "hg19": {
        "hgvs_genomic_description": "NC_000017.10:g.7579472G>C",
        "vcf": {
          "chr": "chr17",
          "pos": "7579472",
          "ref": "G",
          "alt": "C"
        }
      },
      "grch38": {
        "hgvs_genomic_description": "NC_000017.11:g.7676154G>C",
        "vcf": {
          "chr": "17",
          "pos": "7676154",
          "ref": "G",
          "alt": "C"
        }
      },
      "hg38": {
        "hgvs_genomic_description": "NC_000017.11:g.7676154G>C",
        "vcf": {
          "chr": "chr17",
          "pos": "7676154",
          "ref": "G",
          "alt": "C"
        }
      }
    },
    "variant_exonic_positions": {
      "NC_000017.10": {
        "start_exon": "4",
        "end_exon": "4"
      },
      "NC_000017.11": {
        "start_exon": "4",
        "end_exon": "4"
      }
    },
    "reference_sequence_records": {
      "transcript": "https://www.ncbi.nlm.nih.gov/nuccore/NM_000546.6",
      "protein": "https://www.ncbi.nlm.nih.gov/nuccore/NP_000537.3"
    }
  },
  "metadata": {
    "variantvalidator_version": "4.0.0",
    "variantvalidator_hgvs_version": "4.0.0",
    "vvta_version": "vvta_2025_02",
    "vvseqrepo_db": "VV_SR_2025_02/master",
    "vvdb_version": "vvdb_2025_3"
  }
}

---

Behaviour

• Validates HGVS, VCF and pseudo-VCF syntax and structure
• Performs correction of minor, unambiguous errors where possible
• Maps variants to transcript and predicted protein consequences
• Returns genomic, transcript and protein representations
• Performs liftover according to the liftover_level setting
• Reports warnings, corrections and sequence mismatches

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Notes

• Multiple inputs
• "17-50198002-C-A|17-50197802-G-T" pipe-delimited string
• ["17-50198002-C-A", "17-50198002-C-T"]
• Maximum of 10 variants per request
• Transcript selection behaviour is defined in Transcript Selection
• liftover_level controls whether additional genome assembly mappings are returned:
• True (default) — perform full liftover to alternative genome assemblies
• primary — perform liftover but exclude alternative scaffold mappings
• False — disable liftover and return only the requested genome assembly
• Uses the RefSeq transcript set only
• More computationally intensive than /VariantFormatter_v2
• Prefer mane_select, mane, or explicit transcript IDs for improved performance
• Avoid all and raw unless full transcript enumeration is required
• For Ensembl-based validation, use /VariantValidator_ensembl