TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7928	24007;24008;24009	chr2:178719710;178719709;178719708	chr2:179584437;179584436;179584435
N2AB	7611	23056;23057;23058	chr2:178719710;178719709;178719708	chr2:179584437;179584436;179584435
N2A	6684	20275;20276;20277	chr2:178719710;178719709;178719708	chr2:179584437;179584436;179584435
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-64
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.3329
• 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/Q	rs770121355	-0.439	0.689	N	0.243	0.302	0.329540904979	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	1.78E-05	0
E/Q	rs770121355	-0.439	0.689	N	0.243	0.302	0.329540904979	gnomAD-4.0.0	4.77435E-06	None	None	None	None	N	None	0	2.28655E-05	None	0	0	None	0	0	5.71759E-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	0.1519	likely_benign	0.1588	benign	-0.509	Destabilizing	0.248	N	0.324	neutral	N	0.498165179	None	None	N
E/C	0.8316	likely_pathogenic	0.8695	pathogenic	-0.33	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
E/D	0.3255	likely_benign	0.35	ambiguous	-0.532	Destabilizing	0.961	D	0.463	neutral	N	0.498708157	None	None	N
E/F	0.7365	likely_pathogenic	0.7941	pathogenic	0.099	Stabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
E/G	0.282	likely_benign	0.3037	benign	-0.793	Destabilizing	0.961	D	0.595	neutral	N	0.521170959	None	None	N
E/H	0.5732	likely_pathogenic	0.6219	pathogenic	0.382	Stabilizing	0.996	D	0.561	neutral	None	None	None	None	N
E/I	0.245	likely_benign	0.3076	benign	0.242	Stabilizing	0.996	D	0.721	prob.delet.	None	None	None	None	N
E/K	0.166	likely_benign	0.1926	benign	0.188	Stabilizing	0.248	N	0.28	neutral	D	0.533288831	None	None	N
E/L	0.2709	likely_benign	0.3276	benign	0.242	Stabilizing	0.97	D	0.597	neutral	None	None	None	None	N
E/M	0.3438	ambiguous	0.3935	ambiguous	0.261	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/N	0.4422	ambiguous	0.489	ambiguous	-0.521	Destabilizing	0.996	D	0.516	neutral	None	None	None	None	N
E/P	0.2981	likely_benign	0.2941	benign	0.012	Stabilizing	0.999	D	0.647	neutral	None	None	None	None	N
E/Q	0.1387	likely_benign	0.1486	benign	-0.401	Destabilizing	0.689	D	0.243	neutral	N	0.499228362	None	None	N
E/R	0.2977	likely_benign	0.3293	benign	0.578	Stabilizing	0.942	D	0.494	neutral	None	None	None	None	N
E/S	0.3276	likely_benign	0.3483	ambiguous	-0.678	Destabilizing	0.942	D	0.459	neutral	None	None	None	None	N
E/T	0.2969	likely_benign	0.3421	ambiguous	-0.424	Destabilizing	0.97	D	0.579	neutral	None	None	None	None	N
E/V	0.1497	likely_benign	0.1795	benign	0.012	Stabilizing	0.961	D	0.587	neutral	N	0.499837473	None	None	N
E/W	0.9041	likely_pathogenic	0.929	pathogenic	0.403	Stabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/Y	0.6508	likely_pathogenic	0.7138	pathogenic	0.388	Stabilizing	0.999	D	0.715	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.