TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24949	75070;75071;75072	chr2:178571287;178571286;178571285	chr2:179436014;179436013;179436012
N2AB	23308	70147;70148;70149	chr2:178571287;178571286;178571285	chr2:179436014;179436013;179436012
N2A	22381	67366;67367;67368	chr2:178571287;178571286;178571285	chr2:179436014;179436013;179436012
N2B	15884	47875;47876;47877	chr2:178571287;178571286;178571285	chr2:179436014;179436013;179436012
Novex-1	16009	48250;48251;48252	chr2:178571287;178571286;178571285	chr2:179436014;179436013;179436012
Novex-2	16076	48451;48452;48453	chr2:178571287;178571286;178571285	chr2:179436014;179436013;179436012
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: Fn3-69
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.4917
• 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	rs1179463518	-1.295	0.993	N	0.664	0.555	0.461671691612	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66058E-04
E/G	rs1179463518	-1.295	0.993	N	0.664	0.555	0.461671691612	gnomAD-4.0.0	1.59182E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-05	0
E/Q	rs753903335	-0.765	0.997	N	0.635	0.31	0.368369118721	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/Q	rs753903335	-0.765	0.997	N	0.635	0.31	0.368369118721	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
E/Q	rs753903335	-0.765	0.997	N	0.635	0.31	0.368369118721	gnomAD-4.0.0	6.57903E-06	None	None	None	None	N	None	2.41581E-05	0	None	0	0	None	0	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
E/A	0.6086	likely_pathogenic	0.6491	pathogenic	-0.927	Destabilizing	0.977	D	0.617	neutral	N	0.485905095	None	None	N
E/C	0.9793	likely_pathogenic	0.9816	pathogenic	-0.515	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/D	0.2436	likely_benign	0.295	benign	-1.329	Destabilizing	0.117	N	0.205	neutral	N	0.470074353	None	None	N
E/F	0.9785	likely_pathogenic	0.9834	pathogenic	-0.321	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/G	0.5916	likely_pathogenic	0.6364	pathogenic	-1.35	Destabilizing	0.993	D	0.664	neutral	N	0.489058647	None	None	N
E/H	0.9377	likely_pathogenic	0.9431	pathogenic	-0.663	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
E/I	0.8827	likely_pathogenic	0.9032	pathogenic	0.251	Stabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
E/K	0.7869	likely_pathogenic	0.8007	pathogenic	-0.879	Destabilizing	0.977	D	0.529	neutral	N	0.513747773	None	None	N
E/L	0.8437	likely_pathogenic	0.872	pathogenic	0.251	Stabilizing	0.998	D	0.772	deleterious	None	None	None	None	N
E/M	0.8764	likely_pathogenic	0.8935	pathogenic	0.828	Stabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
E/N	0.7368	likely_pathogenic	0.7777	pathogenic	-1.351	Destabilizing	0.99	D	0.685	prob.neutral	None	None	None	None	N
E/P	0.8806	likely_pathogenic	0.8843	pathogenic	-0.12	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
E/Q	0.534	ambiguous	0.5367	ambiguous	-1.151	Destabilizing	0.997	D	0.635	neutral	N	0.477876471	None	None	N
E/R	0.8636	likely_pathogenic	0.8698	pathogenic	-0.635	Destabilizing	0.998	D	0.731	prob.delet.	None	None	None	None	N
E/S	0.7039	likely_pathogenic	0.7504	pathogenic	-1.788	Destabilizing	0.983	D	0.582	neutral	None	None	None	None	N
E/T	0.8355	likely_pathogenic	0.8619	pathogenic	-1.426	Destabilizing	0.998	D	0.698	prob.neutral	None	None	None	None	N
E/V	0.7421	likely_pathogenic	0.7797	pathogenic	-0.12	Destabilizing	0.997	D	0.745	deleterious	N	0.487906558	None	None	N
E/W	0.9922	likely_pathogenic	0.9935	pathogenic	-0.125	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/Y	0.9601	likely_pathogenic	0.968	pathogenic	-0.069	Destabilizing	1.0	D	0.729	prob.delet.	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.