Case#: P1, M, Age of Report: N/A, Ethnicity: N/A.

CasePresentingHPOs: HP:0000490 (Deeply set eye/Ocular depression), HP:0000680 (Delayed eruption of primary teeth/Teeth delay), HP:0000540 (Hypermetropia/Hyperopia), HP:0000483 (Astigmatism), HP:0007485 (Absence of subcutaneous fat/Lack of subcutaneous fat), HP:0000831 (Insulin-resistant diabetes mellitus), HP:0000325 (Triangular face/Facial dysmorphim Triangular shape), HP:0000430 (Underdeveloped nasal alae/thin alae nasi), HP:0000331 (Short chin/Small chin), HP:0000369 (Low-set ears), HP:0012371 (Hyperplasia of midface/Mild midface hypoplasia), HP:0000347 (Micrognathia), HP:0100678 (Premature skin wrinkling/Thin, wrinkled skin), HP:0001256 (Intellectual disability, mild/Mild impairment),

CaseHPOFreeText: Proband was noted to have readily visible veins and delayed bone age.

CaseNotHPOs: N/A.

CaseNotHPOFreeText: N/A.

CasePreviousTesting: N/A.

CaseMethod1: N/A.

CaseMethod2: N/A.

CaseGenotypingMethod: WES.

Variant: NM_181523.3:c.1615_1617del (p.Ile539del).

ClinVar: 60761.

CAID: CA344796.

gnomAD: N/A.

VariantEvidence: N/A.

CaseAddInfo: N/A.

CasePMIDs: N/A.

Case#: P2, M, Age of Report: N/A, Ethnicity: N/A.

CasePresentingHPOs: HP:0000490 (Deeply set eye/Ocular depression), HP:0000680 (Delayed eruption of primary teeth/Teeth delay), HP:0007485 (Absence of subcutaneous fat/Lack of subcutaneous fat), HP:0000831 (Insulin-resistant diabetes mellitus), HP:0000325 (Triangular face/Facial dysmorphim Triangular shape), HP:0000430 (Underdeveloped nasal alae/thin alae nasi), HP:0000331 (Short chin/Small chin), HP:0000369 (Low-set ears), HP:0012371 (Hyperplasia of midface/Mild midface hypoplasia), HP:0000347 (Micrognathia), HP:0100678 (Premature skin wrinkling/Thin, wrinkled skin), HP:0001256 (Intellectual disability, mild/Mild impairment),

CaseHPOFreeText: Proband was noted to have readily visible veins and delayed bone age.

CaseNotHPOs: N/A.

CaseNotHPOFreeText: N/A..

CasePreviousTesting: N/A.

CaseMethod1: N/A.

CaseMethod2: N/A.

CaseGenotypingMethod: WES.

Variant: NM_181523.3:c.1465G>A (p.Glu489Lys).

ClinVar: 60762.

CAID: CA344798.

gnomAD: N/A.

VariantEvidence: N/A.

CaseAddInfo: N/A.

CasePMIDs: N/A.

Case#: P3, F, Age of Report: N/A, Ethnicity: N/A.

CasePresentingHPOs: HP:0001382 (Joint hypermobility/Hyperextensibility of joints), HP:0000490 (Deeply set eye/Ocular depression), HP:0000558 (Rieger anomaly), HP:0000680 (Delayed eruption of primary teeth/Teeth delay), HP:0000540 (Hypermetropia/Hyperopia), HP:0000483 (Astigmatism), HP:0000565 (Esotropia), HP:0007485 (Absence of subcutaneous fat/Lack of subcutaneous fat), HP:0000831 (Insulin-resistant diabetes mellitus), HP:0000325 (Triangular face/Facial dysmorphim Triangular shape), HP:0011220 (Prominent forehead), HP:0000430 (Underdeveloped nasal alae/thin alae nasi), HP:0000331 (Short chin/Small chin), HP:0000369 (Low-set ears), HP:0012371 (Hyperplasia of midface/Mild midface hypoplasia), HP:0000347 (Micrognathia), HP:0000138 (Ovarian cyst), HP:0001256 (Intellectual disability, mild/Mild impairment), HP:0003100 (Slender long bone/Gracile long bones)

CaseHPOFreeText: Proband was noted to have delayed bone age and mild impairment and/or speech delay

CaseNotHPOs: N/A.

CaseNotHPOFreeText: N/A..

CasePreviousTesting: N/A.

CaseMethod1: N/A.

CaseMethod2: N/A.

CaseGenotypingMethod: WES.

Variant: NM_181523.3:c.1945C>T (p.Arg649Trp).

ClinVar: 60763.

CAID: CA344799.

gnomAD: N/A.

VariantEvidence: N/A.

CaseAddInfo: N/A.

CasePMIDs: N/A.

Case#: P4, M, Age of Report: N/A, Ethnicity: N/A.

CasePresentingHPOs: HP:0004322 (Short stature), HP:0004325 (Decreased body weight), HP:0040195 (Decreased head circumference), HP:0000490 (Deeply set eye/Ocular depression), HP:0000680 (Delayed eruption of primary teeth/Teeth delay), HP:0000540 (Hypermetropia/Hyperopia), HP:0007485 (Absence of subcutaneous fat/Lack of subcutaneous fat), HP:0000325 (Triangular face/Facial dysmorphim Triangular shape), HP:0011220 (Prominent forehead), HP:0000430 (Underdeveloped nasal alae/thin alae nasi), HP:0000331 (Short chin/Small chin), HP:0000369 (Low-set ears), HP:0012371 (Hyperplasia of midface/Mild midface hypoplasia), HP:0000347 (Micrognathia), HP:0100678 (Premature skin wrinkling/Thin, wrinkled skin),

CaseHPOFreeText: Proband was noted to readily visible veins, normal mental development.

Proband was not evaluated for insulin resistance, ovarian cysts, delayed bone age or gracile long bones.

CaseNotHPOs: N/A.

CaseNotHPOFreeText: Proband was noted to not have hyperextensibility of joints, inguinal hernia, Rieger anomaly, astigmatism, myopia, esotropia, diabetes, frequent illnesses, mild impairment and/or speech delay.

CasePreviousTesting: N/A.

CaseMethod1: N/A.

CaseMethod2: N/A.

CaseGenotypingMethod: WES.

Variant: NM_181523.3:c.1945C>T (p.Arg649Trp).

ClinVar: 60763.

CAID: CA344799.

gnomAD: N/A.

VariantEvidence: N/A.

CaseAddInfo: N/A.

CasePMIDs: N/A.

Case#: P5, F, Age of Report: N/A, Ethnicity: N/A.

CasePresentingHPOs: HP:0001382 (Joint hypermobility/Hyperextensibility of joints), HP:0000490 (Deeply set eye/Ocular depression), HP:0000558 (Rieger anomaly), HP:0000680 (Delayed eruption of primary teeth/Teeth delay), HP:0000545 (Myopia), HP:0007485 (Absence of subcutaneous fat/Lack of subcutaneous fat), HP:0000831 (Insulin-resistant diabetes mellitus), HP:0000325 (Triangular face/Facial dysmorphim Triangular shape), HP:0011220 (Prominent forehead), HP:0000430 (Underdeveloped nasal alae/thin alae nasi), HP:0000331 (Short chin/Small chin), HP:0000369 (Low-set ears), HP:0012371 (Hyperplasia of midface/Mild midface hypoplasia), HP:0000347 (Micrognathia),

CaseHPOFreeText: Proband was noted to have insulin resistance, frequent illnesses, ovarian cysts, normal mental development,

Proband was not evaluated for delayed bone age or gracile long bones.

CaseNotHPOs: N/A.

CaseNotHPOFreeText: Proband was noted to not have inguinal hernia, hyperopia, astigmatism, esotropia, thin, wrinkled skin, readily visible veins, mild impairment and/or speech delay.

CasePreviousTesting: N/A.

CaseMethod1: N/A.

CaseMethod2: N/A.

CaseGenotypingMethod: WES.

Variant: NM_181523.3:c.1945C>T (p.Arg649Trp).

ClinVar: 60763.

CAID: CA344799.

gnomAD: N/A.

VariantEvidence: N/A.

CaseAddInfo: N/A.

CasePMIDs: N/A.

Case#: P6, M, Age of Report: N/A, Ethnicity: N/A.

CasePresentingHPOs: HP:0000490 (Deeply set eye/Ocular depression), HP:0000325 (Triangular face/Facial dysmorphim Triangular shape), HP:0011220 (Prominent forehead), HP:0000430 (Underdeveloped nasal alae/thin alae nasi), HP:0000331 (Short chin/Small chin), HP:0000369 (Low-set ears), HP:0012371 (Hyperplasia of midface/Mild midface hypoplasia), (Micrognathia),

CaseHPOFreeText: Proband was not evaluated for inguinal hernia, Rieger anomaly, teeth delay, hyperopia, astigmatism, myopia, esotropia, lack of subcutaneous fat, insulin resistance, diabetes, thin, wrinkled skin, readily visible veins, frequent illnesses, ovarian cysts, normal mental development, mild impairment and/or speech delay, delayed bone age or gracile long bones.

CaseNotHPOs: N/A.

CaseNotHPOFreeText: Proband was noted to not have hyperextensibility of joints,

CasePreviousTesting: N/A.

CaseMethod1: N/A.

CaseMethod2: N/A.

CaseGenotypingMethod: WES.

Variant: NM_181523.3:c.1945C>T (p.Arg649Trp).

ClinVar: 60763.

CAID: CA344799.

gnomAD: N/A.

VariantEvidence: N/A.

CaseAddInfo: N/A.

CasePMIDs: N/A.

Case#: P7, F, Age of Report: N/A, Ethnicity: N/A.

CasePresentingHPOs: HP:0000680 (Delayed eruption of primary teeth/Teeth delay), HP:0000483 (Astigmatism), HP:0007485 (Absence of subcutaneous fat/Lack of subcutaneous fat), HP:0000831 (Insulin-resistant diabetes mellitus), HP:0011220 (Prominent forehead), HP:0000430 (Underdeveloped nasal alae/thin alae nasi), HP:0000331 (Short chin/Small chin), HP:0000369 (Low-set ears), HP:0000347 (Micrognathia),

CaseHPOFreeText: : Proband was noted to have insulin resistance, ovarian cysts, normal mental development,

Proband was not evaluated for hyperextensibility of joints, ocular depression, hyperopia, myopia, esotropia, Triangular face, Mild midface hypoplasia, frequent illnesses, delayed bone age or gracile long bones.

CaseNotHPOs: N/A.

CaseNotHPOFreeText: Proband was noted to not have inguinal hernia, Rieger anomaly, thin, wrinkled skin, readily visible veins, mild impairment and/or speech delay,

CasePreviousTesting: N/A.

CaseMethod1: N/A.

CaseMethod2: N/A.

CaseGenotypingMethod: WES.

Variant: NM_181523.3:c.1945C>T (p.Arg649Trp).

ClinVar: 60763.

CAID: CA344799.

gnomAD: N/A.

VariantEvidence: N/A.

CaseAddInfo: N/A.

CasePMIDs: N/A.

Case#: P8, F, Age of Report: N/A, Ethnicity: N/A.

CasePresentingHPOs: HP:0007485 (Absence of subcutaneous fat/Lack of subcutaneous fat), HP:0000831 (Insulin-resistant diabetes mellitus), HP:0000325 (Triangular face/Facial dysmorphim Triangular shape), HP:0011220 (Prominent forehead), HP:0000430 (Underdeveloped nasal alae/thin alae nasi), HP:0000331 (Short chin/Small chin), HP:0000369 (Low-set ears), HP:0012371 (Hyperplasia of midface/Mild midface hypoplasia), HP:0000347 (Micrognathia),

CaseHPOFreeText: Proband was noted to have insulin resistance, thin, wrinkled skin, readily visible veins, frequent illnesses, normal mental development,

Proband was not evaluated for hyperextensibility of joints, teeth delay, hyperopia, astigmatism, myopia, esotropia, ovarian cysts, delayed bone age or gracile long bones.

CaseNotHPOs: N/A.

CaseNotHPOFreeText: Proband was noted to not have inguinal hernia, Rieger anomaly, mild impairment and/or speech delay.

CasePreviousTesting: N/A.

CaseMethod1: N/A.

CaseMethod2: N/A.

CaseGenotypingMethod: WES.

Variant: NM_181523.3:c.1943dup (p.Arg649ProfsTer5).

ClinVar: 60764.

CAID: CA344800.

gnomAD: N/A.

VariantEvidence: N/A.

CaseAddInfo: N/A.

CasePMIDs: N/A.

Case#: P9, M, Age of Report: N/A, Ethnicity: N/A.

CasePresentingHPOs: HP:0004325 (Decreased body weight), HP:0007485 (Absence of subcutaneous fat/Lack of subcutaneous fat), HP:0000831 (Insulin-resistant diabetes mellitus), HP:0000325 (Triangular face/Facial dysmorphim Triangular shape), HP:0000430 (Underdeveloped nasal alae/thin alae nasi), HP:0000331 (Short chin/Small chin), HP:0000369 (Low-set ears), HP:0000347 (Micrognathia),

CaseHPOFreeText: Proband was noted to have insulin resistance, normal mental development, mild impairment and/or speech delay,

Proband was not evaluated for height/length, occipitofrontal circumference, hyperextensibility of joints, teeth delay, hyperopia, astigmatism, myopia, esotropia, thin, wrinkled skin, readily visible veins, frequent illnesses, ovarian cysts, delayed bone age or gracile long bones.

CaseNotHPOs: N/A.

CaseNotHPOFreeText: Proband was noted to not have inguinal hernia, ocular depression, Rieger anomaly, Prominent forehead, Mild midface hypoplasia,

CasePreviousTesting: N/A.

CaseMethod1: N/A.

CaseMethod2: N/A.

CaseGenotypingMethod: WES.

Variant: NM_181523.3:c.1892G>A (p.Arg631Gln).

ClinVar: 126459.

CAID: CA347796.

gnomAD: N/A.

VariantEvidence: N/A.

CaseAddInfo: N/A.

CasePMIDs: N/A.