TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32293	97102;97103;97104	chr2:178543096;178543095;178543094	chr2:179407823;179407822;179407821
N2AB	30652	92179;92180;92181	chr2:178543096;178543095;178543094	chr2:179407823;179407822;179407821
N2A	29725	89398;89399;89400	chr2:178543096;178543095;178543094	chr2:179407823;179407822;179407821
N2B	23228	69907;69908;69909	chr2:178543096;178543095;178543094	chr2:179407823;179407822;179407821
Novex-1	23353	70282;70283;70284	chr2:178543096;178543095;178543094	chr2:179407823;179407822;179407821
Novex-2	23420	70483;70484;70485	chr2:178543096;178543095;178543094	chr2:179407823;179407822;179407821
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-123
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.5407
• 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
T/P	rs200555813	-0.014	0.999	N	0.735	0.38	None	gnomAD-4.0.0	9.65802E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.26939E-05	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
T/A	0.0786	likely_benign	0.0746	benign	-0.124	Destabilizing	0.603	D	0.283	neutral	N	0.473455801	None	None	N
T/C	0.4316	ambiguous	0.3948	ambiguous	-0.38	Destabilizing	1.0	D	0.699	prob.delet.	None	None	None	None	N
T/D	0.4093	ambiguous	0.374	ambiguous	0.161	Stabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	N
T/E	0.3306	likely_benign	0.3203	benign	0.076	Stabilizing	0.999	D	0.701	prob.delet.	None	None	None	None	N
T/F	0.2538	likely_benign	0.2314	benign	-0.774	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
T/G	0.2186	likely_benign	0.2015	benign	-0.192	Destabilizing	0.993	D	0.673	prob.neutral	None	None	None	None	N
T/H	0.2615	likely_benign	0.2515	benign	-0.372	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
T/I	0.2127	likely_benign	0.1989	benign	-0.068	Destabilizing	0.999	D	0.735	deleterious	N	0.466071958	None	None	N
T/K	0.2418	likely_benign	0.2414	benign	-0.255	Destabilizing	0.999	D	0.675	prob.neutral	N	0.481960641	None	None	N
T/L	0.1076	likely_benign	0.1007	benign	-0.068	Destabilizing	0.993	D	0.651	prob.neutral	None	None	None	None	N
T/M	0.0894	likely_benign	0.0887	benign	-0.161	Destabilizing	1.0	D	0.698	prob.delet.	None	None	None	None	N
T/N	0.1309	likely_benign	0.1223	benign	-0.117	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
T/P	0.1491	likely_benign	0.1303	benign	-0.061	Destabilizing	0.999	D	0.735	deleterious	N	0.519748238	None	None	N
T/Q	0.2322	likely_benign	0.232	benign	-0.286	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
T/R	0.1929	likely_benign	0.1933	benign	-0.009	Destabilizing	0.999	D	0.727	deleterious	N	0.47074357	None	None	N
T/S	0.1096	likely_benign	0.1015	benign	-0.274	Destabilizing	0.983	D	0.503	neutral	N	0.469876778	None	None	N
T/V	0.15	likely_benign	0.1434	benign	-0.061	Destabilizing	0.993	D	0.497	neutral	None	None	None	None	N
T/W	0.586	likely_pathogenic	0.5571	ambiguous	-0.877	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
T/Y	0.2884	likely_benign	0.2752	benign	-0.542	Destabilizing	1.0	D	0.795	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.