[Table, Spectrum of Phenotypes Associated with SETBP1 Pathogenic Variants] - GeneReviews®

Designation	Associated Pathogenic Variants	Comment
*Schinzel-Giedion syndrome (SGS) phenotypic continuum (topic of this GeneReview)*	Classic SGS	Gain-of-function pathogenic variants in mutational hot spot (i.e., a 12-base-pair region in exon 4 encoding a canonical degron)	Severe phenotype consistent w/original SGS clinical diagnostic criteria ¹
Atypical SGS	Gain-of-function pathogenic variants adjacent to – but not within –mutational hot spot	Broad spectrum of clinical features of variable severity that partially overlap w/classic SGS Atypical SGS is milder than classic SGS.
SETBP1-related disorders (not SGS or SETBP1-HD)	Missense pathogenic variants w/unknown functional effects that are not adjacent to mutational hot spot	"SETBP1-related disorders" may be used to refer to phenotypes that are not consistent w/SGS or SETBP1-HD caused by SETBP1 pathogenic variants that do not result in loss of function and are not within or near the SGS mutational hot spot. Note: "SETBP1-related disorders" has also been used to refer to all phenotypes associated w/SETBP1 pathogenic variants. See Genetically Related Disorders.
*SETBP1* Haploinsufficiency Disorder *(SETBP1-HD)*	Loss-of-function pathogenic variants (truncating variants / SETBP1-specific deletions)	See Genetically Related Disorders.

Designation

Associated Pathogenic Variants

Comment

Schinzel-Giedion syndrome (SGS) phenotypic continuum (topic of this GeneReview)

Classic SGS

Gain-of-function pathogenic variants in mutational hot spot (i.e., a 12-base-pair region in exon 4 encoding a canonical degron)

Severe phenotype consistent w/original SGS clinical diagnostic criteria ¹

Atypical SGS

Gain-of-function pathogenic variants adjacent to – but not within –mutational hot spot

Broad spectrum of clinical features of variable severity that partially overlap w/classic SGS
Atypical SGS is milder than classic SGS.

SETBP1-related disorders (not SGS or SETBP1-HD)

Missense pathogenic variants w/unknown functional effects that are not adjacent to mutational hot spot

"SETBP1-related disorders" may be used to refer to phenotypes that are not consistent w/SGS or SETBP1-HD caused by SETBP1 pathogenic variants that do not result in loss of function and are not within or near the SGS mutational hot spot.
Note: "SETBP1-related disorders" has also been used to refer to all phenotypes associated w/SETBP1 pathogenic variants.
See Genetically Related Disorders.

SETBP1 Haploinsufficiency Disorder (SETBP1-HD)

Loss-of-function pathogenic variants (truncating variants / SETBP1-specific deletions)

See Genetically Related Disorders.

From: Schinzel-Giedion Syndrome

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Adam MP, Feldman J, Mirzaa GM, et al., editors.

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