TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20631	62116;62117;62118	chr2:178589834;178589833;178589832	chr2:179454561;179454560;179454559
N2AB	18990	57193;57194;57195	chr2:178589834;178589833;178589832	chr2:179454561;179454560;179454559
N2A	18063	54412;54413;54414	chr2:178589834;178589833;178589832	chr2:179454561;179454560;179454559
N2B	11566	34921;34922;34923	chr2:178589834;178589833;178589832	chr2:179454561;179454560;179454559
Novex-1	11691	35296;35297;35298	chr2:178589834;178589833;178589832	chr2:179454561;179454560;179454559
Novex-2	11758	35497;35498;35499	chr2:178589834;178589833;178589832	chr2:179454561;179454560;179454559
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-37
• Domain position: 63
• Structural Position: 96
• Q(SASA): 0.3693
• Predicted PPI site: I

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/D	None	None	0.425	N	0.421	0.18	0.115124310173	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
N/K	rs940775890	0.083	0.01	N	0.155	0.173	0.0986583533028	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
N/K	rs940775890	0.083	0.01	N	0.155	0.173	0.0986583533028	gnomAD-4.0.0	3.42163E-06	None	None	None	None	I	None	0	0	None	0	2.52321E-05	None	0	0	3.59837E-06	0	0
N/S	rs2049834334	None	0.023	N	0.19	0.153	0.104622674875	gnomAD-4.0.0	1.59188E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02462E-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
N/A	0.2561	likely_benign	0.2548	benign	-0.395	Destabilizing	0.329	N	0.391	neutral	None	None	None	None	I
N/C	0.3394	likely_benign	0.3332	benign	0.303	Stabilizing	0.995	D	0.591	neutral	None	None	None	None	I
N/D	0.2231	likely_benign	0.205	benign	0.11	Stabilizing	0.425	N	0.421	neutral	N	0.423373698	None	None	I
N/E	0.5209	ambiguous	0.4604	ambiguous	0.099	Stabilizing	0.495	N	0.416	neutral	None	None	None	None	I
N/F	0.6353	likely_pathogenic	0.6339	pathogenic	-0.622	Destabilizing	0.944	D	0.617	neutral	None	None	None	None	I
N/G	0.29	likely_benign	0.3197	benign	-0.607	Destabilizing	0.329	N	0.415	neutral	None	None	None	None	I
N/H	0.1357	likely_benign	0.1292	benign	-0.578	Destabilizing	0.013	N	0.278	neutral	N	0.465595113	None	None	I
N/I	0.3728	ambiguous	0.3288	benign	0.083	Stabilizing	0.927	D	0.625	neutral	N	0.478218866	None	None	I
N/K	0.4182	ambiguous	0.3418	ambiguous	-0.017	Destabilizing	0.01	N	0.155	neutral	N	0.429571738	None	None	I
N/L	0.3747	ambiguous	0.3274	benign	0.083	Stabilizing	0.704	D	0.535	neutral	None	None	None	None	I
N/M	0.4795	ambiguous	0.4762	ambiguous	0.392	Stabilizing	0.981	D	0.575	neutral	None	None	None	None	I
N/P	0.3845	ambiguous	0.2528	benign	-0.048	Destabilizing	0.007	N	0.401	neutral	None	None	None	None	I
N/Q	0.3754	ambiguous	0.3428	ambiguous	-0.448	Destabilizing	0.704	D	0.505	neutral	None	None	None	None	I
N/R	0.483	ambiguous	0.3914	ambiguous	0.008	Stabilizing	0.543	D	0.428	neutral	None	None	None	None	I
N/S	0.087	likely_benign	0.0898	benign	-0.283	Destabilizing	0.023	N	0.19	neutral	N	0.497007451	None	None	I
N/T	0.1495	likely_benign	0.1423	benign	-0.138	Destabilizing	0.473	N	0.42	neutral	N	0.460606721	None	None	I
N/V	0.32	likely_benign	0.2882	benign	-0.048	Destabilizing	0.704	D	0.597	neutral	None	None	None	None	I
N/W	0.8706	likely_pathogenic	0.8466	pathogenic	-0.567	Destabilizing	0.995	D	0.623	neutral	None	None	None	None	I
N/Y	0.2574	likely_benign	0.2463	benign	-0.324	Destabilizing	0.863	D	0.603	neutral	N	0.519847026	None	None	I

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.