TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9041	27346;27347;27348	chr2:178712904;178712903;178712902	chr2:179577631;179577630;179577629
N2AB	8724	26395;26396;26397	chr2:178712904;178712903;178712902	chr2:179577631;179577630;179577629
N2A	7797	23614;23615;23616	chr2:178712904;178712903;178712902	chr2:179577631;179577630;179577629
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-76
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.2925
• 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
I/M	rs890920556	None	0.11	N	0.243	0.03	0.369867359543	gnomAD-4.0.0	1.3689E-06	None	None	None	None	N	None	5.97729E-05	0	None	0	0	None	0	0	0	0	0
I/V	rs1395755933	None	0.001	N	0.154	0.087	0.363356657567	gnomAD-4.0.0	4.10656E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39764E-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
I/A	0.1359	likely_benign	0.1884	benign	-1.554	Destabilizing	0.061	N	0.284	neutral	None	None	None	None	N
I/C	0.6095	likely_pathogenic	0.7191	pathogenic	-1.135	Destabilizing	0.94	D	0.499	neutral	None	None	None	None	N
I/D	0.5161	ambiguous	0.6563	pathogenic	-0.7	Destabilizing	0.418	N	0.571	neutral	None	None	None	None	N
I/E	0.3295	likely_benign	0.4212	ambiguous	-0.7	Destabilizing	0.418	N	0.544	neutral	None	None	None	None	N
I/F	0.1104	likely_benign	0.1359	benign	-1.156	Destabilizing	0.213	N	0.449	neutral	N	0.507065021	None	None	N
I/G	0.4962	ambiguous	0.6347	pathogenic	-1.856	Destabilizing	0.418	N	0.52	neutral	None	None	None	None	N
I/H	0.2953	likely_benign	0.3817	ambiguous	-1.029	Destabilizing	0.94	D	0.536	neutral	None	None	None	None	N
I/K	0.1907	likely_benign	0.2468	benign	-0.859	Destabilizing	0.01	N	0.373	neutral	None	None	None	None	N
I/L	0.0902	likely_benign	0.112	benign	-0.805	Destabilizing	None	N	0.135	neutral	N	0.478531626	None	None	N
I/M	0.082	likely_benign	0.0943	benign	-0.714	Destabilizing	0.11	N	0.243	neutral	N	0.477262189	None	None	N
I/N	0.2223	likely_benign	0.3035	benign	-0.69	Destabilizing	0.351	N	0.586	neutral	N	0.474528529	None	None	N
I/P	0.6967	likely_pathogenic	0.8194	pathogenic	-1.023	Destabilizing	0.94	D	0.595	neutral	None	None	None	None	N
I/Q	0.2723	likely_benign	0.3507	ambiguous	-0.885	Destabilizing	0.716	D	0.593	neutral	None	None	None	None	N
I/R	0.1259	likely_benign	0.1706	benign	-0.337	Destabilizing	0.264	N	0.583	neutral	None	None	None	None	N
I/S	0.1795	likely_benign	0.2391	benign	-1.393	Destabilizing	0.021	N	0.325	neutral	N	0.446611209	None	None	N
I/T	0.0868	likely_benign	0.1118	benign	-1.275	Destabilizing	0.007	N	0.191	neutral	N	0.4273693	None	None	N
I/V	0.0621	likely_benign	0.0652	benign	-1.023	Destabilizing	0.001	N	0.154	neutral	N	0.397185253	None	None	N
I/W	0.5493	ambiguous	0.6824	pathogenic	-1.16	Destabilizing	0.983	D	0.557	neutral	None	None	None	None	N
I/Y	0.3567	ambiguous	0.4377	ambiguous	-0.914	Destabilizing	0.836	D	0.553	neutral	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.