TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26241	78946;78947;78948	chr2:178567411;178567410;178567409	chr2:179432138;179432137;179432136
N2AB	24600	74023;74024;74025	chr2:178567411;178567410;178567409	chr2:179432138;179432137;179432136
N2A	23673	71242;71243;71244	chr2:178567411;178567410;178567409	chr2:179432138;179432137;179432136
N2B	17176	51751;51752;51753	chr2:178567411;178567410;178567409	chr2:179432138;179432137;179432136
Novex-1	17301	52126;52127;52128	chr2:178567411;178567410;178567409	chr2:179432138;179432137;179432136
Novex-2	17368	52327;52328;52329	chr2:178567411;178567410;178567409	chr2:179432138;179432137;179432136
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-137
• Domain position: 49
• Structural Position: 122
• Q(SASA): 0.2379
• 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
E/G	None	None	0.988	N	0.649	0.496	0.469333501611	gnomAD-4.0.0	6.88882E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02695E-07	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
E/A	0.3733	ambiguous	0.3309	benign	-0.778	Destabilizing	0.958	D	0.481	neutral	N	0.495340795	None	None	N
E/C	0.927	likely_pathogenic	0.9125	pathogenic	-0.411	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/D	0.274	likely_benign	0.2194	benign	-1.163	Destabilizing	0.979	D	0.375	neutral	D	0.525362781	None	None	N
E/F	0.8818	likely_pathogenic	0.8528	pathogenic	-0.093	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/G	0.5125	ambiguous	0.4473	ambiguous	-1.175	Destabilizing	0.988	D	0.649	neutral	N	0.505749276	None	None	N
E/H	0.6605	likely_pathogenic	0.6147	pathogenic	-0.38	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
E/I	0.4574	ambiguous	0.398	ambiguous	0.313	Stabilizing	0.995	D	0.808	deleterious	None	None	None	None	N
E/K	0.362	ambiguous	0.33	benign	-0.441	Destabilizing	0.958	D	0.432	neutral	N	0.504523362	None	None	N
E/L	0.6466	likely_pathogenic	0.579	pathogenic	0.313	Stabilizing	0.991	D	0.773	deleterious	None	None	None	None	N
E/M	0.6054	likely_pathogenic	0.549	ambiguous	0.736	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/N	0.5098	ambiguous	0.4363	ambiguous	-1.059	Destabilizing	0.995	D	0.676	prob.neutral	None	None	None	None	N
E/P	0.989	likely_pathogenic	0.9869	pathogenic	-0.029	Destabilizing	0.086	N	0.33	neutral	None	None	None	None	N
E/Q	0.2171	likely_benign	0.1987	benign	-0.887	Destabilizing	0.994	D	0.58	neutral	N	0.511124047	None	None	N
E/R	0.5555	ambiguous	0.5293	ambiguous	-0.197	Destabilizing	0.995	D	0.683	prob.neutral	None	None	None	None	N
E/S	0.3854	ambiguous	0.3298	benign	-1.372	Destabilizing	0.968	D	0.505	neutral	None	None	None	None	N
E/T	0.3532	ambiguous	0.2998	benign	-1.026	Destabilizing	0.991	D	0.663	neutral	None	None	None	None	N
E/V	0.3089	likely_benign	0.2691	benign	-0.029	Destabilizing	0.994	D	0.707	prob.neutral	D	0.532096752	None	None	N
E/W	0.9691	likely_pathogenic	0.9611	pathogenic	0.192	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/Y	0.8446	likely_pathogenic	0.8119	pathogenic	0.191	Stabilizing	0.998	D	0.777	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.