TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15010	45253;45254;45255	chr2:178621894;178621893;178621892	chr2:179486621;179486620;179486619
N2AB	13369	40330;40331;40332	chr2:178621894;178621893;178621892	chr2:179486621;179486620;179486619
N2A	12442	37549;37550;37551	chr2:178621894;178621893;178621892	chr2:179486621;179486620;179486619
N2B	5945	18058;18059;18060	chr2:178621894;178621893;178621892	chr2:179486621;179486620;179486619
Novex-1	6070	18433;18434;18435	chr2:178621894;178621893;178621892	chr2:179486621;179486620;179486619
Novex-2	6137	18634;18635;18636	chr2:178621894;178621893;178621892	chr2:179486621;179486620;179486619
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-101
• Domain position: 69
• Structural Position: 153
• Q(SASA): 0.3202
• 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/K	None	None	0.999	D	0.665	0.398	0.394536629495	gnomAD-4.0.0	1.59483E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86397E-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
E/A	0.2535	likely_benign	0.2854	benign	-0.928	Destabilizing	0.999	D	0.701	prob.neutral	N	0.504937772	None	None	N
E/C	0.9382	likely_pathogenic	0.9564	pathogenic	-0.236	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
E/D	0.2967	likely_benign	0.343	ambiguous	-0.925	Destabilizing	0.999	D	0.545	neutral	N	0.513755328	None	None	N
E/F	0.8494	likely_pathogenic	0.8957	pathogenic	-0.774	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/G	0.3676	ambiguous	0.4169	ambiguous	-1.223	Destabilizing	1.0	D	0.745	deleterious	D	0.706351134	None	None	N
E/H	0.715	likely_pathogenic	0.7943	pathogenic	-1.013	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
E/I	0.4708	ambiguous	0.5925	pathogenic	-0.142	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/K	0.2647	likely_benign	0.3587	ambiguous	-0.205	Destabilizing	0.999	D	0.665	neutral	D	0.534174752	None	None	N
E/L	0.5494	ambiguous	0.6392	pathogenic	-0.142	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/M	0.5941	likely_pathogenic	0.6822	pathogenic	0.405	Stabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
E/N	0.4523	ambiguous	0.5776	pathogenic	-0.608	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/P	0.8257	likely_pathogenic	0.854	pathogenic	-0.384	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/Q	0.2303	likely_benign	0.2818	benign	-0.543	Destabilizing	1.0	D	0.641	neutral	N	0.501731892	None	None	N
E/R	0.4242	ambiguous	0.4988	ambiguous	-0.113	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/S	0.3495	ambiguous	0.4237	ambiguous	-0.869	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
E/T	0.3426	ambiguous	0.4354	ambiguous	-0.614	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/V	0.2913	likely_benign	0.3656	ambiguous	-0.384	Destabilizing	1.0	D	0.785	deleterious	N	0.502501557	None	None	N
E/W	0.9577	likely_pathogenic	0.9679	pathogenic	-0.563	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/Y	0.8084	likely_pathogenic	0.8675	pathogenic	-0.509	Destabilizing	1.0	D	0.769	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.