Documentation / Family Analysis / Inheritance Patterns

Inheritance Pattern Classification in Clinical Trios

Folklore assigns one inheritance-pattern label to each variant present in the proband. The label summarizes existing detector outputs, trio genotypes, chromosome context, and proband sex in a form that can be displayed and filtered consistently.

This step is derivational. It does not replace de novo detection, compound-heterozygous phasing, segregation scoring, ACMG classification, or clinical interpretation.

Authoritative Evidence Remains Separate

The inheritance-pattern column is a summary. The underlying de novo tier, inference basis, compound-heterozygous partner, phase source, confidence state, genotypes, and segregation fields remain the authoritative technical evidence.

How to Read a Pattern

Each proband variant receives at most one summary label. The label is derived consistently from the available family evidence so that results can be grouped and filtered, but it is not a substitute for reviewing the underlying genotypes and detector outputs.

Where more than one family observation could describe the same row, Folklore uses a stable precedence to produce one label. The detailed de novo, compound-heterozygous, segregation, and per-member fields remain available for interpretation.

Pattern Categories

Stored Pattern	Technical Basis	Clinical Review Boundary
de_novo_high	De novo candidate with high technical confidence.	Review the underlying parental genotype, depth, quality, and PS2 boundary.
de_novo_low	De novo candidate with unresolved or sub-threshold parental evidence.	Origin remains insufficiently established for high-confidence use.
compound_het_high	A compound-heterozygous partner is recorded with high confidence.	Inspect both variants, parental origin, phase source, and PM3 requirements.
compound_het_low	A compound-heterozygous partner is recorded with low confidence.	Phase remains unresolved or limited by parental genotype data.
x_linked_recessive_male	Male proband carries an X variant and the mother is heterozygous.	Sex, X-chromosome region, genotype representation, phenotype, and gene mechanism still require review.
x_linked_recessive_female_homozygous	Female proband is homozygous on X, with maternal and paternal variant carriage.	This rare configuration requires careful pedigree and genotype review.
x_linked_dominant	The proband carries an X variant and exactly one parent carries it.	The categorical rule does not fully enforce every sex-specific transmission constraint.
mitochondrial	The proband and mother carry the mitochondrial variant.	The label does not assess heteroplasmy, tissue distribution, or pathogenicity.
autosomal_recessive_homozygous	The proband is homozygous alternate on an autosome and both parents are heterozygous.	Review gene-disease validity, phenotype fit, and the classifications of the allele.
autosomal_dominant_inherited	The proband is heterozygous on an autosome and exactly one parent carries the variant.	Affected status, penetrance, age of onset, and phenocopies remain clinically relevant.
unclear_parents_no_call	The proband carries the variant and both parental genotypes are no-calls.	No parental-origin conclusion can be made from the available calls.
unclear	The row matches none of the defined categories.	This can include atypical, inconsistent, unresolved, or cis-associated configurations.

Parent-Only Rows

A site present only in a parent has no proband variant index. Such a row is not assigned an inheritance pattern and remains null rather than being forced into an unclear category.

Sex-Gated X-Linked Categories

X-linked categories require proband sex to be recorded as male or female. When sex is absent, Folklore suppresses the X-linked labels and allows the row to fall through to another applicable category or to unclear.

Sex-chromosome labels also account for chromosome context, including the distinction between pseudoautosomal and non-pseudoautosomal regions. Ambiguous or incomplete states are handled conservatively rather than being forced into an X-linked category.

Pattern Versus Pathogenicity

An inheritance label describes how the observed genotypes fit a categorical transmission rule. It does not establish that the variant causes disease, that the gene explains the phenotype, or that an ACMG criterion should be applied.

A benign variant can match a recognizable inheritance pattern. A clinically relevant variant can also remain unclear when parental genotypes, sex, phase, or family structure are insufficient.

Relationship to ACMG Classification

An inheritance pattern does not automatically upgrade, downgrade, or replace the proband ACMG classification.

Family evidence remains available through the dedicated detector and segregation fields. Any criterion application and final classification decision remain separate.

Unavailable and Legacy Results

If a pattern cannot be derived, the family evidence remains available through the underlying detector, genotype, and segregation fields. The absence of a summary label does not erase those results.

Legacy trio analyses can also have a null pattern because they were processed before categorical derivation was introduced. A null value must therefore be read with the algorithm version and evidence summary.