TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16365	49318;49319;49320	chr2:178614304;178614303;178614302	chr2:179479031;179479030;179479029
N2AB	14724	44395;44396;44397	chr2:178614304;178614303;178614302	chr2:179479031;179479030;179479029
N2A	13797	41614;41615;41616	chr2:178614304;178614303;178614302	chr2:179479031;179479030;179479029
N2B	7300	22123;22124;22125	chr2:178614304;178614303;178614302	chr2:179479031;179479030;179479029
Novex-1	7425	22498;22499;22500	chr2:178614304;178614303;178614302	chr2:179479031;179479030;179479029
Novex-2	7492	22699;22700;22701	chr2:178614304;178614303;178614302	chr2:179479031;179479030;179479029
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-6
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.35
• 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
N/S	rs1424335711	None	0.004	N	0.309	0.093	0.0482279557977	gnomAD-4.0.0	6.84568E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99792E-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
N/A	0.1679	likely_benign	0.1468	benign	-1.051	Destabilizing	0.48	N	0.545	neutral	None	None	None	None	N
N/C	0.2237	likely_benign	0.2087	benign	-0.315	Destabilizing	0.98	D	0.794	deleterious	None	None	None	None	N
N/D	0.2297	likely_benign	0.2191	benign	-1.188	Destabilizing	0.41	N	0.457	neutral	N	0.459051485	None	None	N
N/E	0.4976	ambiguous	0.4573	ambiguous	-1.108	Destabilizing	0.48	N	0.547	neutral	None	None	None	None	N
N/F	0.6543	likely_pathogenic	0.611	pathogenic	-0.975	Destabilizing	0.929	D	0.789	deleterious	None	None	None	None	N
N/G	0.2681	likely_benign	0.2462	benign	-1.35	Destabilizing	0.48	N	0.461	neutral	None	None	None	None	N
N/H	0.1408	likely_benign	0.1357	benign	-1.082	Destabilizing	0.908	D	0.731	prob.delet.	N	0.48060892	None	None	N
N/I	0.3258	likely_benign	0.3068	benign	-0.3	Destabilizing	0.83	D	0.78	deleterious	D	0.546121443	None	None	N
N/K	0.4076	ambiguous	0.3656	ambiguous	-0.38	Destabilizing	0.41	N	0.557	neutral	N	0.392729822	None	None	N
N/L	0.3217	likely_benign	0.2943	benign	-0.3	Destabilizing	0.866	D	0.709	prob.delet.	None	None	None	None	N
N/M	0.3772	ambiguous	0.3515	ambiguous	0.283	Stabilizing	0.993	D	0.752	deleterious	None	None	None	None	N
N/P	0.333	likely_benign	0.3186	benign	-0.523	Destabilizing	0.866	D	0.743	deleterious	None	None	None	None	N
N/Q	0.3689	ambiguous	0.3389	benign	-1.213	Destabilizing	0.866	D	0.713	prob.delet.	None	None	None	None	N
N/R	0.4048	ambiguous	0.3649	ambiguous	-0.242	Destabilizing	0.866	D	0.707	prob.neutral	None	None	None	None	N
N/S	0.0641	likely_benign	0.0593	benign	-1.057	Destabilizing	0.004	N	0.309	neutral	N	0.428945269	None	None	N
N/T	0.1574	likely_benign	0.1414	benign	-0.801	Destabilizing	0.41	N	0.487	neutral	N	0.478909054	None	None	N
N/V	0.2653	likely_benign	0.2445	benign	-0.523	Destabilizing	0.866	D	0.747	deleterious	None	None	None	None	N
N/W	0.8026	likely_pathogenic	0.7896	pathogenic	-0.713	Destabilizing	0.993	D	0.817	deleterious	None	None	None	None	N
N/Y	0.2481	likely_benign	0.2232	benign	-0.489	Destabilizing	0.908	D	0.776	deleterious	D	0.585944444	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.