TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21765	65518;65519;65520	chr2:178583889;178583888;178583887	chr2:179448616;179448615;179448614
N2AB	20124	60595;60596;60597	chr2:178583889;178583888;178583887	chr2:179448616;179448615;179448614
N2A	19197	57814;57815;57816	chr2:178583889;178583888;178583887	chr2:179448616;179448615;179448614
N2B	12700	38323;38324;38325	chr2:178583889;178583888;178583887	chr2:179448616;179448615;179448614
Novex-1	12825	38698;38699;38700	chr2:178583889;178583888;178583887	chr2:179448616;179448615;179448614
Novex-2	12892	38899;38900;38901	chr2:178583889;178583888;178583887	chr2:179448616;179448615;179448614
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-46
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5458
• 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/A	rs1430045391	-0.645	0.999	N	0.751	0.353	0.406120066682	gnomAD-2.1.1	4.49E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.85048E-04
E/A	rs1430045391	-0.645	0.999	N	0.751	0.353	0.406120066682	gnomAD-4.0.0	6.98304E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.31498E-06	0	3.38352E-05

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	0.3036	likely_benign	0.2757	benign	-0.606	Destabilizing	0.999	D	0.751	deleterious	N	0.470621543	None	None	N
E/C	0.9225	likely_pathogenic	0.8921	pathogenic	-0.385	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
E/D	0.2811	likely_benign	0.2284	benign	-0.773	Destabilizing	0.999	D	0.564	neutral	N	0.467418765	None	None	N
E/F	0.8958	likely_pathogenic	0.8591	pathogenic	-0.004	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
E/G	0.4952	ambiguous	0.468	ambiguous	-0.928	Destabilizing	1.0	D	0.779	deleterious	N	0.495411295	None	None	N
E/H	0.6593	likely_pathogenic	0.6008	pathogenic	-0.028	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
E/I	0.4682	ambiguous	0.4116	ambiguous	0.256	Stabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
E/K	0.2683	likely_benign	0.2596	benign	-0.207	Destabilizing	0.999	D	0.645	neutral	N	0.460777292	None	None	N
E/L	0.5924	likely_pathogenic	0.5478	ambiguous	0.256	Stabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
E/M	0.5992	likely_pathogenic	0.5503	ambiguous	0.415	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
E/N	0.4919	ambiguous	0.4243	ambiguous	-0.769	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/P	0.9802	likely_pathogenic	0.9819	pathogenic	-0.01	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/Q	0.1982	likely_benign	0.1788	benign	-0.647	Destabilizing	1.0	D	0.696	prob.neutral	N	0.498180887	None	None	N
E/R	0.4016	ambiguous	0.3868	ambiguous	0.135	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/S	0.4008	ambiguous	0.3497	ambiguous	-0.983	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
E/T	0.3747	ambiguous	0.3147	benign	-0.713	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
E/V	0.2619	likely_benign	0.2335	benign	-0.01	Destabilizing	1.0	D	0.829	deleterious	N	0.501914626	None	None	N
E/W	0.9634	likely_pathogenic	0.9538	pathogenic	0.27	Stabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
E/Y	0.833	likely_pathogenic	0.7866	pathogenic	0.258	Stabilizing	1.0	D	0.845	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.