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Clinician orientation sheet

NM_018489.3:c.3808C>T

Concise orientation only. Dates, normal findings, uncertainty, source boundaries, and longitudinal context remain in the complete profile.

Molecular result and profile context

Report transcript + cDNA
NM_018489.3:c.3808C>T
Report protein consequence
p.Arg1270*
Zygosity
Heterozygous
Molecular consequence
Nonsense / stop-gain
Laboratory classification
Pathogenic
Classification source
Owner-approved current public/governed decision
Inheritance
De novo
Relevant additional finding
Not reported in this public profile
Normalized MANE/map notation
NM_018489.3:c.3808C>T · NP_060959.2:p.Arg1270*
Variant type
Nonsense / stop-gain
Sex
Female
Age group
Ages 16–20
Protein position
Premature stop · aa 1,270

Approved public summary

This is the story of an adolescent girl in the 16–20 age group with a de novo pathogenic ASH1L nonsense variant, developmental and cognitive differences, speech-language impairment, hypotonia, early left-sided motor weakness, strabismus, and severe epilepsy dominated by daily absence seizures around waking. Two later tonic-clonic seizures caused falls and required hospital care. After vagus nerve stimulation, her family observed fewer daily absences and a meaningful increase in how awake and active she seemed, although her absence epilepsy remained uncontrolled. In March, her family reported another episode that they described as syncopal; they reported that the VNS stopped the seizure. Her family has also observed a recent, uncharacteristic shift toward aggressive and rebellious behavior after a period in which she had been calm and well-behaved.