Table 1.

Disease-causing heterozygous PPARG variants in subjects with FPLD3

Patients (n)	Variant cDNA level	Variant protein level	rs number	Clinvar prediction	Functional score [7]	References
1	c.282delG	p.K94Nfs*4	NA	NA	—	—
1	c.421G>C	p.V141L	NA	NA	−3.5	—
1	c.452C>G	p.Y151C	rs1354592503	Pathogenic	−4.2	[10, 11]
1	c.480+120G>C	(?)	NA	NA	—	—
1	c.580C>T	p.R194W	rs121909146	Pathogenic	−5.4	[12]
2	c.641C>T	p.P214L	NA	NA	−0.48	—
3	c.670G>T	p.E224*	NA	NA	—	—
1	c.971T>C	p.I324T	rs1378972597	Pathogenic	−2.57	—
1	c.1154G>A	p.R385Q	rs140204299	Uncertain significance	−1.4	[7]
3	c.1159C>T	p.P387S	NA	NA	−4.2	[7, 9]
2	c.1184A>G	p.K395R	NA	NA	−1.16	[7, 9]
6	c.1273C>T	p.R425C	rs72551364	Pathogenic	−5.37	[5]
1	c.1313A>C	p.Q438P	NA	Uncertain significance	−4.9	[7, 9]
2	c.1393C>T	p.Q465*	NA	NA	—	—
1	c.1480+1G>A	(?)	NA	NA	—	—
4	c.1484C>T	p.P495L	rs121909244	Pathogenic	−5.58	[13–15]
1	c.1495delG	p.E499Rfs*12	NA	NA	—	—

Five variants were null or splice site variants. Eleven were missense variants, of which 5 were classified as “pathogenic” and 2 of “uncertain significance” by Clinvar. The 2 variants with “uncertain significance” have been published before. One variant is a novel intronic variant not present in the gnomAD database. For the 4 missense variants that had no information in Clinvar, we looked at the functional score according to Majithia et al [7]. All had negative scores. Two of them had functional scores ≤3.5, which has increased probability of lipodystrophy, and 1 of them, p.P387S, has been previously published by 2 groups. There was evidence of segregation in 3 family members for p.K395R and in 2 family members for p.P214L.

Abbreviation: NA, not available.