TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18760	56503;56504;56505	chr2:178599623;178599622;178599621	chr2:179464350;179464349;179464348
N2AB	17119	51580;51581;51582	chr2:178599623;178599622;178599621	chr2:179464350;179464349;179464348
N2A	16192	48799;48800;48801	chr2:178599623;178599622;178599621	chr2:179464350;179464349;179464348
N2B	9695	29308;29309;29310	chr2:178599623;178599622;178599621	chr2:179464350;179464349;179464348
Novex-1	9820	29683;29684;29685	chr2:178599623;178599622;178599621	chr2:179464350;179464349;179464348
Novex-2	9887	29884;29885;29886	chr2:178599623;178599622;178599621	chr2:179464350;179464349;179464348
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-116
• Domain position: 73
• Structural Position: 152
• Q(SASA): 0.2249
• 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/R	None	None	0.83	D	0.793	0.726	0.748157190483	gnomAD-4.0.0	1.59638E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88629E-05	0	0	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	0.1222	likely_benign	0.1282	benign	-0.723	Destabilizing	0.002	N	0.468	neutral	D	0.561357685	None	None	N
G/C	0.3658	ambiguous	0.4125	ambiguous	-0.888	Destabilizing	0.974	D	0.81	deleterious	D	0.626745898	None	None	N
G/D	0.721	likely_pathogenic	0.8029	pathogenic	-1.901	Destabilizing	0.83	D	0.798	deleterious	D	0.584552652	None	None	N
G/E	0.8061	likely_pathogenic	0.8626	pathogenic	-1.806	Destabilizing	0.866	D	0.797	deleterious	None	None	None	None	N
G/F	0.9063	likely_pathogenic	0.9109	pathogenic	-0.681	Destabilizing	0.929	D	0.817	deleterious	None	None	None	None	N
G/H	0.8655	likely_pathogenic	0.8861	pathogenic	-1.816	Destabilizing	0.993	D	0.795	deleterious	None	None	None	None	N
G/I	0.8599	likely_pathogenic	0.8926	pathogenic	0.163	Stabilizing	0.866	D	0.805	deleterious	None	None	None	None	N
G/K	0.9349	likely_pathogenic	0.9485	pathogenic	-1.237	Destabilizing	0.866	D	0.797	deleterious	None	None	None	None	N
G/L	0.8158	likely_pathogenic	0.8298	pathogenic	0.163	Stabilizing	0.764	D	0.806	deleterious	None	None	None	None	N
G/M	0.824	likely_pathogenic	0.8593	pathogenic	0.042	Stabilizing	0.98	D	0.807	deleterious	None	None	None	None	N
G/N	0.7166	likely_pathogenic	0.7873	pathogenic	-1.211	Destabilizing	0.929	D	0.785	deleterious	None	None	None	None	N
G/P	0.9937	likely_pathogenic	0.9938	pathogenic	-0.088	Destabilizing	0.866	D	0.799	deleterious	None	None	None	None	N
G/Q	0.812	likely_pathogenic	0.8465	pathogenic	-1.149	Destabilizing	0.929	D	0.795	deleterious	None	None	None	None	N
G/R	0.8405	likely_pathogenic	0.861	pathogenic	-1.255	Destabilizing	0.83	D	0.793	deleterious	D	0.610292568	None	None	N
G/S	0.1397	likely_benign	0.187	benign	-1.506	Destabilizing	0.41	N	0.699	prob.neutral	D	0.626140485	None	None	N
G/T	0.4823	ambiguous	0.5599	ambiguous	-1.317	Destabilizing	0.764	D	0.793	deleterious	None	None	None	None	N
G/V	0.7014	likely_pathogenic	0.756	pathogenic	-0.088	Destabilizing	0.709	D	0.807	deleterious	D	0.626745898	None	None	N
G/W	0.8981	likely_pathogenic	0.8907	pathogenic	-1.423	Destabilizing	0.993	D	0.763	deleterious	None	None	None	None	N
G/Y	0.8609	likely_pathogenic	0.8667	pathogenic	-0.866	Destabilizing	0.98	D	0.821	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.