TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32656	98191;98192;98193	chr2:178540200;178540199;178540198	chr2:179404927;179404926;179404925
N2AB	31015	93268;93269;93270	chr2:178540200;178540199;178540198	chr2:179404927;179404926;179404925
N2A	30088	90487;90488;90489	chr2:178540200;178540199;178540198	chr2:179404927;179404926;179404925
N2B	23591	70996;70997;70998	chr2:178540200;178540199;178540198	chr2:179404927;179404926;179404925
Novex-1	23716	71371;71372;71373	chr2:178540200;178540199;178540198	chr2:179404927;179404926;179404925
Novex-2	23783	71572;71573;71574	chr2:178540200;178540199;178540198	chr2:179404927;179404926;179404925
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-126
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.6785
• Predicted PPI site: I

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
K/N	None	None	1.0	N	0.707	0.327	0.185906805712	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
K/A	0.4841	ambiguous	0.4425	ambiguous	-0.037	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	I
K/C	0.8015	likely_pathogenic	0.7838	pathogenic	-0.413	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
K/D	0.7724	likely_pathogenic	0.7199	pathogenic	0.141	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
K/E	0.4034	ambiguous	0.3635	ambiguous	0.159	Stabilizing	0.999	D	0.613	neutral	N	0.472378366	None	None	I
K/F	0.9025	likely_pathogenic	0.8753	pathogenic	-0.244	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	I
K/G	0.603	likely_pathogenic	0.5503	ambiguous	-0.228	Destabilizing	1.0	D	0.581	neutral	None	None	None	None	I
K/H	0.4712	ambiguous	0.4498	ambiguous	-0.383	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
K/I	0.5544	ambiguous	0.5042	ambiguous	0.387	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	I
K/L	0.4876	ambiguous	0.4509	ambiguous	0.387	Stabilizing	1.0	D	0.581	neutral	None	None	None	None	I
K/M	0.381	ambiguous	0.3599	ambiguous	0.051	Stabilizing	1.0	D	0.659	neutral	N	0.51532664	None	None	I
K/N	0.6206	likely_pathogenic	0.5647	pathogenic	0.041	Stabilizing	1.0	D	0.707	prob.neutral	N	0.478981838	None	None	I
K/P	0.668	likely_pathogenic	0.6323	pathogenic	0.273	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	I
K/Q	0.2216	likely_benign	0.2126	benign	-0.073	Destabilizing	1.0	D	0.694	prob.neutral	N	0.501914626	None	None	I
K/R	0.0933	likely_benign	0.0912	benign	-0.06	Destabilizing	0.999	D	0.571	neutral	N	0.435729706	None	None	I
K/S	0.6182	likely_pathogenic	0.5656	pathogenic	-0.449	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	I
K/T	0.3093	likely_benign	0.2812	benign	-0.279	Destabilizing	1.0	D	0.662	neutral	N	0.454445966	None	None	I
K/V	0.4542	ambiguous	0.4141	ambiguous	0.273	Stabilizing	1.0	D	0.623	neutral	None	None	None	None	I
K/W	0.8746	likely_pathogenic	0.8555	pathogenic	-0.279	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
K/Y	0.7874	likely_pathogenic	0.7503	pathogenic	0.077	Stabilizing	1.0	D	0.636	neutral	None	None	None	None	I

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.