Table 1.

Non-synonymous variants found in the IRS2 gene of participants with severe insulin resistance (total SIR, n=161; Europid SIR, n=114) and Europid controls (n=173)

Participant	Phenotype	SNP	PolyPhena / SIFTb	Genotype	Ethnicity	Fasting glucose (mmol/l)	Fasting insulin (pmol/l)	BMI (kg/m2)
SIR1	SIR, pseudoacromegaly	c.233G>A p.S78N	Benign / Tolerated	GA	Asian	5.6	212	44.6
SIR2	SIR, pseudoacromegaly	c.1498C>G p.L500V	Benign / Tolerated	CG	Asian	6.0	264	39.7
SIR3	SIR short stature	c.1570A>G p.I524V	Benign / Affect protein function	AG	Turkish	4.9	1358	19
SIR4	SIR, pseudoacromegaly	c.2485C>T p.P829S	Benign / Tolerated	CT	Ashkena zy	5.1	507	25.5
SIR5	SIR	c.2566G>A p.A856T	Benign / Tolerated	GA	Europid	4.7	333	28
SIR6	SIR FPLD1	c.2834C>T p.S945F	Benign / Affect protein function	CT	Europid	5.5	155	obese
SIR7	SIR, pseudoacromegaly	c.3424G>C p.G1142R	Possibly damaging / Affect protein function	GC	Europid	8.5	880	47.3
SIR8	SIR, pseudoacromegaly	c.3983A>G p.H1328R	Possibly damaging / Affect protein function	AG	Europid	6.8	246	37.3
Control 1	Healthy volunteer	c.1379C>T p.P460L and c.3983A>G p.H1328R	Benign / Possibly damaging	CT	Europid	5.5	47	24.6
Control 2	Healthy volunteer	c.3400A>G p.K1134E	Benign / Affect protein function	AG	Europid	5.1	65	31.7
Control 3	Healthy volunteer	c.3788G>T p.G1263V	Probably damaging / Affect protein function	GT	Europid	6.4	43	24.3
Control 4	Healthy volunteer	c.3983A>G p.H1328R	Possibly damaging / Affect protein function	AG	Europid	4.9	45	23.4

^aPolyPhen predicts the possible impact of an amino acid substitution on the structure and function of a protein based on physical and comparative considerations

^bSIFT predicts whether an amino acid substitution affects protein function based on sequence homology and the physical properties of amino acids

FPLD1, familial partial lipodystrophy type 1, Online Mendelian Inheritance in Man (OMIM) (http://www.ncbi.nlm.nih.gov/omim) database ID: 608600; IR, insulin resistance