TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31205	93838;93839;93840	chr2:178548013;178548012;178548011	chr2:179412740;179412739;179412738
N2AB	29564	88915;88916;88917	chr2:178548013;178548012;178548011	chr2:179412740;179412739;179412738
N2A	28637	86134;86135;86136	chr2:178548013;178548012;178548011	chr2:179412740;179412739;179412738
N2B	22140	66643;66644;66645	chr2:178548013;178548012;178548011	chr2:179412740;179412739;179412738
Novex-1	22265	67018;67019;67020	chr2:178548013;178548012;178548011	chr2:179412740;179412739;179412738
Novex-2	22332	67219;67220;67221	chr2:178548013;178548012;178548011	chr2:179412740;179412739;179412738
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-115
• Domain position: 93
• Structural Position: 129
• Q(SASA): 0.4569
• 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
I/V	None	None	0.006	N	0.115	0.059	0.30921473904	gnomAD-4.0.0	1.59126E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-05	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
I/A	0.4042	ambiguous	0.3945	ambiguous	-1.249	Destabilizing	0.355	N	0.393	neutral	None	None	None	None	N
I/C	0.7117	likely_pathogenic	0.6868	pathogenic	-0.779	Destabilizing	0.991	D	0.395	neutral	None	None	None	None	N
I/D	0.7635	likely_pathogenic	0.7246	pathogenic	-0.617	Destabilizing	0.966	D	0.604	neutral	None	None	None	None	N
I/E	0.5947	likely_pathogenic	0.5549	ambiguous	-0.656	Destabilizing	0.905	D	0.563	neutral	None	None	None	None	N
I/F	0.1832	likely_benign	0.1857	benign	-0.897	Destabilizing	0.779	D	0.377	neutral	N	0.450117582	None	None	N
I/G	0.7483	likely_pathogenic	0.7385	pathogenic	-1.519	Destabilizing	0.905	D	0.531	neutral	None	None	None	None	N
I/H	0.5667	likely_pathogenic	0.5393	ambiguous	-0.687	Destabilizing	0.991	D	0.557	neutral	None	None	None	None	N
I/K	0.5058	ambiguous	0.4498	ambiguous	-0.807	Destabilizing	0.905	D	0.539	neutral	None	None	None	None	N
I/L	0.1118	likely_benign	0.1102	benign	-0.613	Destabilizing	0.001	N	0.119	neutral	N	0.409577681	None	None	N
I/M	0.0991	likely_benign	0.0986	benign	-0.481	Destabilizing	0.779	D	0.487	neutral	N	0.479920414	None	None	N
I/N	0.3146	likely_benign	0.2845	benign	-0.59	Destabilizing	0.956	D	0.546	neutral	N	0.498852891	None	None	N
I/P	0.8068	likely_pathogenic	0.807	pathogenic	-0.792	Destabilizing	0.966	D	0.593	neutral	None	None	None	None	N
I/Q	0.4888	ambiguous	0.4605	ambiguous	-0.805	Destabilizing	0.966	D	0.54	neutral	None	None	None	None	N
I/R	0.4194	ambiguous	0.3492	ambiguous	-0.186	Destabilizing	0.905	D	0.549	neutral	None	None	None	None	N
I/S	0.3743	ambiguous	0.3375	benign	-1.164	Destabilizing	0.877	D	0.489	neutral	N	0.498332816	None	None	N
I/T	0.2047	likely_benign	0.1893	benign	-1.089	Destabilizing	0.501	D	0.369	neutral	N	0.405854224	None	None	N
I/V	0.0754	likely_benign	0.0732	benign	-0.792	Destabilizing	0.006	N	0.115	neutral	N	0.403921145	None	None	N
I/W	0.7924	likely_pathogenic	0.7863	pathogenic	-0.922	Destabilizing	0.991	D	0.65	prob.neutral	None	None	None	None	N
I/Y	0.581	likely_pathogenic	0.5487	ambiguous	-0.702	Destabilizing	0.905	D	0.481	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.