TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1119	3580;3581;3582	chr2:178782237;178782236;178782235	chr2:179646964;179646963;179646962
N2AB	1119	3580;3581;3582	chr2:178782237;178782236;178782235	chr2:179646964;179646963;179646962
N2A	1119	3580;3581;3582	chr2:178782237;178782236;178782235	chr2:179646964;179646963;179646962
N2B	1073	3442;3443;3444	chr2:178782237;178782236;178782235	chr2:179646964;179646963;179646962
Novex-1	1073	3442;3443;3444	chr2:178782237;178782236;178782235	chr2:179646964;179646963;179646962
Novex-2	1073	3442;3443;3444	chr2:178782237;178782236;178782235	chr2:179646964;179646963;179646962
Novex-3	1119	3580;3581;3582	chr2:178782237;178782236;178782235	chr2:179646964;179646963;179646962

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-4
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.3378
• 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
G/D	None	None	1.0	N	0.665	0.566	0.230578612272	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
G/S	rs2092847521	None	1.0	N	0.673	0.486	0.20549828249	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0

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
G/A	0.5222	ambiguous	0.4857	ambiguous	-0.377	Destabilizing	1.0	D	0.589	neutral	N	0.509646541	None	None	N
G/C	0.8445	likely_pathogenic	0.8029	pathogenic	-1.04	Destabilizing	1.0	D	0.683	prob.neutral	D	0.679200197	None	None	N
G/D	0.6531	likely_pathogenic	0.5561	ambiguous	-0.712	Destabilizing	1.0	D	0.665	neutral	N	0.473043797	None	None	N
G/E	0.7901	likely_pathogenic	0.7004	pathogenic	-0.871	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
G/F	0.9685	likely_pathogenic	0.9601	pathogenic	-1.052	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
G/H	0.8841	likely_pathogenic	0.8552	pathogenic	-0.489	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
G/I	0.944	likely_pathogenic	0.9277	pathogenic	-0.538	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
G/K	0.9238	likely_pathogenic	0.8919	pathogenic	-0.94	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
G/L	0.9241	likely_pathogenic	0.9085	pathogenic	-0.538	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
G/M	0.929	likely_pathogenic	0.9159	pathogenic	-0.635	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
G/N	0.5836	likely_pathogenic	0.5396	ambiguous	-0.649	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
G/P	0.9942	likely_pathogenic	0.994	pathogenic	-0.453	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
G/Q	0.7995	likely_pathogenic	0.7575	pathogenic	-0.931	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
G/R	0.8412	likely_pathogenic	0.7769	pathogenic	-0.442	Destabilizing	1.0	D	0.697	prob.neutral	N	0.515764552	None	None	N
G/S	0.2486	likely_benign	0.2155	benign	-0.788	Destabilizing	1.0	D	0.673	neutral	N	0.474505726	None	None	N
G/T	0.6697	likely_pathogenic	0.6243	pathogenic	-0.877	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
G/V	0.8806	likely_pathogenic	0.8513	pathogenic	-0.453	Destabilizing	1.0	D	0.682	prob.neutral	D	0.679200197	None	None	N
G/W	0.9447	likely_pathogenic	0.9287	pathogenic	-1.178	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
G/Y	0.9564	likely_pathogenic	0.9395	pathogenic	-0.86	Destabilizing	1.0	D	0.685	prob.neutral	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.