Dual missense
Two missense events reported in one person, shown only at broad-segment resolution.
01Missenseprotein segment 1,500–1,999
02Missenseprotein segment 2,500–2,969
VARIANT LANDSCAPE
Where ASH1L variants occur—and what types they are.
Molecular-class heat maps show the distribution of loss-of-function, missense, and other positioned records across the 2,969-amino-acid canonical protein. Unrelated recurrence, cross-source matches, familial segregation, dual-variant configurations, public same-residue recurrence, and external provenance remain separate analytic layers.
MOLECULAR-CLASS HEAT MAP
Variant density by protein segment and variant type.
Each number is a positioned provenance record or cohort variant. Darker cells indicate more observations within that molecular class; color is not a severity scale.
External sourcebook222 positioned provenance rows · 200-aa segments
LoF / truncatingMissenseOther
| Molecular class | 1–200 | 201–400 | 401–600 | 601–800 | 801–1,000 | 1,001–1,200 | 1,201–1,400 | 1,401–1,600 | 1,601–1,800 | 1,801–2,000 | 2,001–2,200 | 2,201–2,400 | 2,401–2,600 | 2,601–2,800 | 2,801–2,969 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| LoF / truncating | 1 | 3 | 8 | 6 | 3 | 4 | 16 | 5 | 5 | 2 | 9 | 4 | 9 | 2 | 8 |
| Missense | 10 | 3 | 5 | 5 | 2 | 7 | 18 | 15 | 13 | 4 | 7 | 11 | 17 | 11 | 7 |
| Other | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| All positioned | 11 | 6 | 13 | 11 | 5 | 11 | 35 | 20 | 18 | 6 | 16 | 15 | 26 | 14 | 15 |
Connected cohort — privacy-protected49 LoF/missense people + 5 protein events from 3 complex/mixed people · broad segments
LoF / truncatingMissenseComplex / mixed
| Molecular class | 1–499 | 500–999 | 1,000–1,499 | 1,500–1,999 | 2,000–2,499 | 2,500–2,969 |
|---|---|---|---|---|---|---|
| LoF / truncating | 1 | 6 | 10 | 6 | 8 | 0 |
| Missense | 4 | 7 | 3 | 1 | 1 | 2 |
| Complex / mixed | 0 | 0 | 1 | 1 | 0 | 3 |
| All positioned | 5 | 13 | 14 | 8 | 9 | 5 |
External sourcebook: 222 positioned rows—85 LoF/truncating, 135 missense, and 2 other positioned records. Twelve additional external rows are off-scale or protein-position unavailable.
Connected cohort: the primary map contains 49 LoF/missense people—31 positioned LoF/truncating and 18 missense. A separate overlay contributes five protein-position events from three complex/mixed people: one in-frame deletion plus four consequences from the two dual configurations. That makes 54 plotted events, not 54 people. CNV/deletion, protein-undefined splice/noncoding, and pending records remain off the protein scale.
TWO DUAL CONFIGURATIONS · FOUR BROAD-SEGMENT EVENTS
Both dual configurations remain visible without exposing private coordinates.
Each row is one person. Each tile is one reported protein event placed in a 500-amino-acid segment. The two rows therefore represent two people and four plotted events—not four independent cases.
Missense + nonsense
A missense and stop-gain event reported in one person, shown only at broad-segment resolution.
01Missenseprotein segment 2,500–2,969
02Stop-gainprotein segment 2,500–2,969
49primary protein events from 49 LoF/missense people
+5complex/mixed protein events from 3 people
=54plotted protein events
Why five complex/mixed events? The four broad-segment events above are joined by one connected-cohort in-frame deletion in protein segment 1,000–1,499. Exact connected-cohort coordinates are withheld. The missense-plus-nonsense row is retained as reported; the display does not infer phase, transcript mechanism, or two independent coding events.
RECURRENT & MULTI-VARIANT ARCHITECTURE
Independent recurrence, familial segregation, and dual-variant architecture are different signals.
The connected evidence includes two unrelated loss-of-function pairs, an additional internal-to-physician loss-of-function match, a five-person familial missense cluster, and two within-person dual-variant configurations. Exact private coordinates remain withheld.
unrelated LoF pairs
- Same-stop frameshift pair: one female and one male, from unrelated families.
- Truncating LoF pair: two people of the same sex, from unrelated families.
cross-source LoF match
One internally identified LoF case matches a physician-shared LoF case. The match remains visibly source-traced without exposing either private coordinate.
related missense cases
Five people belong to one familial missense cluster. This is one pedigree and one segregation structure—not five independent recurrence events.
dual-variant individuals
- One person has a missense + missense configuration.
- One person has a truncating + missense configuration.
READ THE STRUCTURE FIRST
Do not add unlike molecular events together.
The two unrelated LoF pairs can support independent recurrence comparison. The cross-source LoF match remains a separately traced evidence structure. The five missense cases support familial segregation and within-family variability. The dual findings require allele-specific inheritance, phase, and functional interpretation. These categories are not one prevalence denominator.
Open the longitudinal framework →PUBLIC SAME-RESIDUE SIGNAL · AMINO ACID 1222
Two public frameshift consequences recur at one protein position.
Four retained public provenance rows resolve to two exact frameshift consequences at residue 1222. Connected-cohort and clinician-shared records remain in broad protein segments and are not asserted here as residue-level matches.
PUBLIC EXACT LAYER
2frameshift consequences
- p.Lys1222GlyfsTer10
- p.Lys1222ArgfsTer11
Four retained public provenance rows point to these two consequences, so duplicated source rows do not become four independent people.
Trace the public source rows below →EXTERNAL DATA SOURCES
Six source groups, one provenance registry.
The external landscape contains 234 retained provenance rows: 222 positioned and 12 off-scale or without a usable protein position. Repeated rows and cross-source overlap are retained as provenance and are not treated as independent people.
SFARI Gene — ASH1L
Largest source bucket in the external molecular sourcebook.
DECIPHER — ASH1L
Thirty-one provenance rows; DECIPHER also contributes 28 of the 50 structured external phenotype summaries.
Literature / online sources
Published cases and other traceable online molecular sources retained as provenance rows.
Simons / SFARI records
Eleven positioned molecular provenance rows from the Simons / SFARI source layer.
Physician / clinician-shared
Restricted provenance rows retained in the totals but not exposed at exact-coordinate resolution.
ClinVar / GenomeConnect
Six public records with structured molecular provenance; selected rows include detailed phenotype summaries.
Privacy boundary
Public database and literature rows retain their public source resolution. Physician / clinician-shared rows and connected-cohort exact coordinates are not displayed. The cohort map remains aggregated into broad protein segments.