TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34984	105175;105176;105177	chr2:178531665;178531664;178531663	chr2:179396392;179396391;179396390
N2AB	33343	100252;100253;100254	chr2:178531665;178531664;178531663	chr2:179396392;179396391;179396390
N2A	32416	97471;97472;97473	chr2:178531665;178531664;178531663	chr2:179396392;179396391;179396390
N2B	25919	77980;77981;77982	chr2:178531665;178531664;178531663	chr2:179396392;179396391;179396390
Novex-1	26044	78355;78356;78357	chr2:178531665;178531664;178531663	chr2:179396392;179396391;179396390
Novex-2	26111	78556;78557;78558	chr2:178531665;178531664;178531663	chr2:179396392;179396391;179396390
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-163
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.2349
• 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/D	rs1434654451	None	0.434	N	0.246	0.077	0.183819452728	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs1434654451	None	0.434	N	0.246	0.077	0.183819452728	gnomAD-4.0.0	8.0552E-06	None	None	None	None	N	None	1.3349E-05	0	None	0	0	None	0	0	8.47545E-06	0	3.20184E-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	0.2137	likely_benign	0.2628	benign	-0.698	Destabilizing	0.998	D	0.589	neutral	N	0.502544636	None	None	N
E/C	0.9559	likely_pathogenic	0.9735	pathogenic	-0.389	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/D	0.3543	ambiguous	0.3749	ambiguous	-0.637	Destabilizing	0.434	N	0.246	neutral	N	0.508894605	None	None	N
E/F	0.9513	likely_pathogenic	0.9688	pathogenic	-0.204	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
E/G	0.3408	ambiguous	0.4394	ambiguous	-0.99	Destabilizing	0.999	D	0.629	neutral	N	0.476822259	None	None	N
E/H	0.8092	likely_pathogenic	0.8689	pathogenic	-0.138	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	N
E/I	0.699	likely_pathogenic	0.7672	pathogenic	0.077	Stabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
E/K	0.3507	ambiguous	0.458	ambiguous	-0.286	Destabilizing	0.998	D	0.49	neutral	N	0.509817325	None	None	N
E/L	0.6916	likely_pathogenic	0.757	pathogenic	0.077	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/M	0.7421	likely_pathogenic	0.7948	pathogenic	0.249	Stabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
E/N	0.5537	ambiguous	0.6102	pathogenic	-0.694	Destabilizing	0.999	D	0.626	neutral	None	None	None	None	N
E/P	0.4232	ambiguous	0.5081	ambiguous	-0.161	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/Q	0.2702	likely_benign	0.3253	benign	-0.586	Destabilizing	0.999	D	0.567	neutral	N	0.494733229	None	None	N
E/R	0.5293	ambiguous	0.6539	pathogenic	0.085	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
E/S	0.4182	ambiguous	0.4768	ambiguous	-0.93	Destabilizing	0.997	D	0.531	neutral	None	None	None	None	N
E/T	0.4778	ambiguous	0.5667	pathogenic	-0.69	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
E/V	0.4515	ambiguous	0.5321	ambiguous	-0.161	Destabilizing	1.0	D	0.727	prob.delet.	D	0.537254643	None	None	N
E/W	0.9836	likely_pathogenic	0.9913	pathogenic	0.054	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/Y	0.8844	likely_pathogenic	0.9276	pathogenic	0.043	Stabilizing	1.0	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.