Clinician orientation sheet

Molecular result and profile context

Report transcript + cDNA

NM_018489.2:c.3838C>T

Report protein consequence

p.Arg1280*

Zygosity

Heterozygous

Molecular consequence

Nonsense / stop-gain

Laboratory classification

Pathogenic

Classification source

Original report reviewed

Inheritance

De novo

Inheritance source

Original report reviewed

Parental testing

The variant was not detected in either tested parent; the report states that germline mosaicism cannot be excluded.

Relevant additional finding

No other nuclear variant possibly associated with the phenotype and no ACMG secondary finding were identified; mitochondrial results were reported separately.

Normalized MANE/map notation

NM_018489.3:c.3838C>T · NP_060959.2:p.Arg1280*

Variant type

Nonsense / stop-gain

Sex

Female

Age group

Ages 11–15

Protein position

Premature stop · aa 1,280

Approved public summary

This is the story of an affectionate, music-loving adolescent girl in the 11–15 age group with a reported de novo ASH1L nonsense variant, intellectual disability, childhood apraxia of speech, epilepsy, severe anxiety, sensory differences, and a history of developmental and school regression. Her earliest seizures were subtle staring events. More recently, her family witnessed two motor or convulsive seizures. After her medication was increased, no further overt motor or convulsive events were reported, while staring events remained part of her history. She learns especially well through songs and jingles, participates in multiple Special Olympics sports, and becomes openly affectionate and eager to connect once she feels comfortable with someone.