Table 3. Clinical Features of Patients With PHTS and Pathogenic and Likely-Pathogenic CNVs.

Patient Identification	Germline PTEN Mutationa	Phenotype Group	Sex	Neurodevelopmental and Cognitive Features	Other Clinical Features
CCF00105	p.Lys164Argfs*3	ASD/DD	Male	Intellectual disability	Thyroid cancer (7 y of age), renal cell cancer (21 y of age), benign skin neoplasm, acral keratoses, trichilemmoma, lipoma, arteriovenous malformation, thyroid nodule
CCF00301	p.Met239Thr	ASD/DD	Male	Intellectual disability	Macrocephaly
CCF00547	Whole gene deletion	ASD/DD	Male	Global DD	Macrocephaly, dysmorphic features, epilepsy, juvenile polyps, tan macules on glans penis and penile shaft, cryptorchidism, mild chordee
CCF03028	Whole gene deletion	ASD/DD	Male	Mental retardation	Macrocephaly, dysmorphic features, juvenile polyposis syndrome, GI polyps, arteriovenous malformation, oral mucosa papilloma, tan macules on glans penis and penile shaft
CCF05681	p.Leu139Phe	ASD/DD	Male	ASD, global DD	Macrocephaly, dysmorphic features, café-au-lait spots
CCF06601	p.Ala39Thr	ASD/DD	Male	ASD, global DD	Macrocephaly, isolated hemihyperplasia, skin tag
CCF08207	p.Cys136Arg	ASD/DD	Female	Variable delay	Macrocephaly, oral mucosa papilloma, lobular breast carcinoma in situ (44 y of age), benign breast disease, goiter, ovarian cysts, skin tag
CCF11952	p.Arg130*	ASD/DD	Male	Global DD	Macrocephaly, hemangioma, lipoma
CCF07685	p.Asn12Thr	ASD/DD	Male	Global DD	Macrocephaly, dysmorphic features
CCF08084	p.Tyr68Cys	ASD/DD	Female	Global DD, anxiety disorder	Macrocephaly and dolicocephaly, café-au-lait spots, ventriculomegaly, Rathke cleft cyst, skin thickening
CCF10918	p.Thr319Asnfs*6	ASD/DD	Female	Mental retardation, global DD	Macrocephaly, dysmorphic features, hirsutism
CCF05270	p.Gly129Glu	No ASD/DD	Female	NA	Macrocephaly, GI polyps, arteriovenous malformation, benign breast disease, colon lipoma, glycogenic acanthosis, goiter, skin tag
CCF13078	p.Thr319*	No ASD/DD	Female	NA	Macrocephaly, GI polyps, benign neurologic neoplasms, benign breast disease, lipoma, neoplasms in vascular tissue, skin papilloma, thyroid nodule
CCF13466	p.Arg335*	No ASD/DD	Male	NA	Macrocephaly and dolicocephaly, Chiari malformation type I, syndactyly (toes 2 and 3), papillomatous papules, multiple melanocytic nevi, nevus flammeus of face, epidermal nevus
CCF01879	p.Arg335*	No ASD/DD (cancer)	Male	NA	Macrocephaly, thyroid cancer (69 y of age), GI polyps, angiolipoma, lipoma, basal cell carcinoma, benign neoplasm of skin, goiter, oral mucosa papilloma, skin papilloma, trichilemmoma
CCF04392	p.Arg233*	No ASD/DD (cancer)	Female	NA	Macrocephaly, thyroid cancer (42 y of age), breast cancer (44 y of age), lobular carcinoma in situ of breast, benign breast disease, benign neoplasm of skin, benign neurologic neoplasms, dermal fibroma, Hashimoto thyroiditis, lipoma

Abbreviations: ASD, autism spectrum disorder; CNV, copy number variation; DD, developmental delay; GI, gastrointestinal; NA, not applicable; PHTS, PTEN hamartoma tumor syndrome.

^aAll mutations have been reported in ClinVar as pathogenic except for 2 unreported mutations (p.Met239Thr and p.Ala39Thr).