TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35441	106546;106547;106548	chr2:178530294;178530293;178530292	chr2:179395021;179395020;179395019
N2AB	33800	101623;101624;101625	chr2:178530294;178530293;178530292	chr2:179395021;179395020;179395019
N2A	32873	98842;98843;98844	chr2:178530294;178530293;178530292	chr2:179395021;179395020;179395019
N2B	26376	79351;79352;79353	chr2:178530294;178530293;178530292	chr2:179395021;179395020;179395019
Novex-1	26501	79726;79727;79728	chr2:178530294;178530293;178530292	chr2:179395021;179395020;179395019
Novex-2	26568	79927;79928;79929	chr2:178530294;178530293;178530292	chr2:179395021;179395020;179395019
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-166
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1142
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
V/F	None	None	0.278	N	0.793	0.239	0.342631996419	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
V/A	0.4133	ambiguous	0.4375	ambiguous	-1.356	Destabilizing	None	N	0.425	neutral	N	0.444068683	None	None	N
V/C	0.8801	likely_pathogenic	0.8891	pathogenic	-0.537	Destabilizing	0.922	D	0.797	deleterious	None	None	None	None	N
V/D	0.9523	likely_pathogenic	0.9599	pathogenic	-1.892	Destabilizing	0.438	N	0.88	deleterious	N	0.460228472	None	None	N
V/E	0.8931	likely_pathogenic	0.9014	pathogenic	-1.602	Destabilizing	0.338	N	0.82	deleterious	None	None	None	None	N
V/F	0.3315	likely_benign	0.3677	ambiguous	-0.617	Destabilizing	0.278	N	0.793	deleterious	N	0.496153729	None	None	N
V/G	0.6108	likely_pathogenic	0.6123	pathogenic	-1.939	Destabilizing	0.052	N	0.848	deleterious	N	0.506928083	None	None	N
V/H	0.9649	likely_pathogenic	0.973	pathogenic	-1.984	Destabilizing	0.922	D	0.885	deleterious	None	None	None	None	N
V/I	0.0771	likely_benign	0.0889	benign	0.301	Stabilizing	None	N	0.288	neutral	N	0.486782097	None	None	N
V/K	0.928	likely_pathogenic	0.9394	pathogenic	-0.668	Destabilizing	0.338	N	0.821	deleterious	None	None	None	None	N
V/L	0.2487	likely_benign	0.2817	benign	0.301	Stabilizing	0.008	N	0.487	neutral	N	0.48747553	None	None	N
V/M	0.2462	likely_benign	0.2726	benign	0.122	Stabilizing	0.338	N	0.694	prob.neutral	None	None	None	None	N
V/N	0.8791	likely_pathogenic	0.9011	pathogenic	-1.179	Destabilizing	0.508	D	0.887	deleterious	None	None	None	None	N
V/P	0.9585	likely_pathogenic	0.9694	pathogenic	-0.227	Destabilizing	0.508	D	0.845	deleterious	None	None	None	None	N
V/Q	0.8904	likely_pathogenic	0.9002	pathogenic	-0.841	Destabilizing	0.508	D	0.851	deleterious	None	None	None	None	N
V/R	0.8857	likely_pathogenic	0.9	pathogenic	-0.99	Destabilizing	0.508	D	0.889	deleterious	None	None	None	None	N
V/S	0.6798	likely_pathogenic	0.7089	pathogenic	-1.732	Destabilizing	0.068	N	0.825	deleterious	None	None	None	None	N
V/T	0.5459	ambiguous	0.5758	pathogenic	-1.286	Destabilizing	0.127	N	0.73	prob.delet.	None	None	None	None	N
V/W	0.9576	likely_pathogenic	0.9668	pathogenic	-1.21	Destabilizing	0.922	D	0.87	deleterious	None	None	None	None	N
V/Y	0.8686	likely_pathogenic	0.889	pathogenic	-0.724	Destabilizing	0.508	D	0.787	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.