TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28954	87085;87086;87087	chr2:178558599;178558598;178558597	chr2:179423326;179423325;179423324
N2AB	27313	82162;82163;82164	chr2:178558599;178558598;178558597	chr2:179423326;179423325;179423324
N2A	26386	79381;79382;79383	chr2:178558599;178558598;178558597	chr2:179423326;179423325;179423324
N2B	19889	59890;59891;59892	chr2:178558599;178558598;178558597	chr2:179423326;179423325;179423324
Novex-1	20014	60265;60266;60267	chr2:178558599;178558598;178558597	chr2:179423326;179423325;179423324
Novex-2	20081	60466;60467;60468	chr2:178558599;178558598;178558597	chr2:179423326;179423325;179423324
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-99
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.265
• 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/T	None	None	None	N	0.151	0.16	0.294206760003	gnomAD-4.0.0	4.77916E-06	None	None	None	None	N	None	0	2.29347E-05	None	0	0	None	1.88509E-05	0	0	0	3.02608E-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
I/A	0.1737	likely_benign	0.1826	benign	-1.712	Destabilizing	0.007	N	0.282	neutral	None	None	None	None	N
I/C	0.4422	ambiguous	0.4646	ambiguous	-1.649	Destabilizing	0.356	N	0.37	neutral	None	None	None	None	N
I/D	0.6128	likely_pathogenic	0.6257	pathogenic	-1.002	Destabilizing	0.214	N	0.494	neutral	None	None	None	None	N
I/E	0.4923	ambiguous	0.5059	ambiguous	-0.968	Destabilizing	0.072	N	0.472	neutral	None	None	None	None	N
I/F	0.1641	likely_benign	0.1777	benign	-1.382	Destabilizing	0.214	N	0.394	neutral	None	None	None	None	N
I/G	0.4058	ambiguous	0.4208	ambiguous	-2.022	Highly Destabilizing	0.072	N	0.434	neutral	None	None	None	None	N
I/H	0.4067	ambiguous	0.429	ambiguous	-1.33	Destabilizing	0.864	D	0.417	neutral	None	None	None	None	N
I/K	0.2941	likely_benign	0.3091	benign	-1.007	Destabilizing	0.055	N	0.469	neutral	N	0.492489853	None	None	N
I/L	0.1073	likely_benign	0.1124	benign	-0.919	Destabilizing	0.002	N	0.215	neutral	N	0.487582679	None	None	N
I/M	0.1038	likely_benign	0.1097	benign	-1.047	Destabilizing	0.171	N	0.433	neutral	N	0.481754493	None	None	N
I/N	0.2136	likely_benign	0.2175	benign	-0.925	Destabilizing	0.214	N	0.492	neutral	None	None	None	None	N
I/P	0.6357	likely_pathogenic	0.6279	pathogenic	-1.155	Destabilizing	0.356	N	0.497	neutral	None	None	None	None	N
I/Q	0.3185	likely_benign	0.3321	benign	-1.084	Destabilizing	0.356	N	0.485	neutral	None	None	None	None	N
I/R	0.2307	likely_benign	0.2426	benign	-0.606	Destabilizing	0.171	N	0.496	neutral	N	0.500666619	None	None	N
I/S	0.1681	likely_benign	0.1707	benign	-1.647	Destabilizing	0.038	N	0.391	neutral	None	None	None	None	N
I/T	0.1116	likely_benign	0.1159	benign	-1.491	Destabilizing	None	N	0.151	neutral	N	0.444293261	None	None	N
I/V	0.0535	likely_benign	0.054	benign	-1.155	Destabilizing	None	N	0.089	neutral	N	0.386396964	None	None	N
I/W	0.7666	likely_pathogenic	0.7967	pathogenic	-1.393	Destabilizing	0.864	D	0.461	neutral	None	None	None	None	N
I/Y	0.4271	ambiguous	0.4544	ambiguous	-1.112	Destabilizing	0.356	N	0.451	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.