Methods

Resource stack

PrimeReplace Atlas uses GRCh38 / GRCh38.p14 coordinates, MANE Select transcript anchors, GENCODE v49 transcript structures, and ClinVar GRCh38 pathogenic/likely pathogenic records.

Variant-to-transcript mapping

ClinVar P/LP records are assigned to MANE/GENCODE transcript coordinates where a gene and transcript structure are available. The release reports both ClinVar gene-variant rows and unique genomic coordinates to support record-redundancy sensitivity review.

Transcript-unit enumeration

The atlas enumerates single-exon units, adjacent exon-block units, and boundary-CDS coverage units. These units are used to summarize record-level coverage and payload/context burden. Boundary-CDS coverage is treated as a transcript-unit architecture descriptor, not as a functional-rescue claim.

Record support gate

Genes with fewer than 20 ClinVar P/LP records are retained but flagged as low-record-burden interpretation-limited. This gate prevents sparse-record genes from being overinterpreted as robust architecture classes.

Architecture labels

Architecture labels summarize how pathogenic-record burden is organized across transcript units. Labels include local compact architecture, boundary-CDS coverage architecture, donor/payload-burden caveat, tumor-predisposition control context, mechanism-complex limitation, diffuse/moderate architecture, and low-record-burden interpretation-limited.

Condition-associated facets

ClinVar condition annotations are parsed into gene-condition record groups where available. High-support groups with recovered transcript-unit coverage are reported as condition-associated record facets. These facets are record-level ClinVar annotation groups, not patient cohorts or prevalence estimates.

Validation and release checks

The public repository includes release checks, a public-language audit, checksum manifest, table inventory, data dictionary, citation metadata, and separate software/data licenses.

PrimeReplace Atlas Browser release 1.0.1.