TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29008	87247;87248;87249	chr2:178558437;178558436;178558435	chr2:179423164;179423163;179423162
N2AB	27367	82324;82325;82326	chr2:178558437;178558436;178558435	chr2:179423164;179423163;179423162
N2A	26440	79543;79544;79545	chr2:178558437;178558436;178558435	chr2:179423164;179423163;179423162
N2B	19943	60052;60053;60054	chr2:178558437;178558436;178558435	chr2:179423164;179423163;179423162
Novex-1	20068	60427;60428;60429	chr2:178558437;178558436;178558435	chr2:179423164;179423163;179423162
Novex-2	20135	60628;60629;60630	chr2:178558437;178558436;178558435	chr2:179423164;179423163;179423162
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: Fn3-99
• Domain position: 67
• Structural Position: 100
• Q(SASA): 0.6705
• 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/D	None	None	0.124	N	0.53	0.119	0.162503812791	gnomAD-4.0.0	1.59132E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85799E-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	0.2728	likely_benign	0.2036	benign	-0.288	Destabilizing	0.157	N	0.587	neutral	None	None	None	None	N
N/C	0.3618	ambiguous	0.2682	benign	0.248	Stabilizing	0.909	D	0.726	prob.delet.	None	None	None	None	N
N/D	0.1362	likely_benign	0.1139	benign	0.184	Stabilizing	0.124	N	0.53	neutral	N	0.493044426	None	None	N
N/E	0.3758	ambiguous	0.3026	benign	0.16	Stabilizing	0.157	N	0.531	neutral	None	None	None	None	N
N/F	0.5579	ambiguous	0.4608	ambiguous	-0.6	Destabilizing	0.726	D	0.679	prob.neutral	None	None	None	None	N
N/G	0.19	likely_benign	0.1519	benign	-0.473	Destabilizing	0.001	N	0.265	neutral	None	None	None	None	N
N/H	0.1281	likely_benign	0.1073	benign	-0.415	Destabilizing	0.667	D	0.489	neutral	N	0.520231028	None	None	N
N/I	0.3869	ambiguous	0.3046	benign	0.111	Stabilizing	0.497	N	0.685	prob.neutral	N	0.503337787	None	None	N
N/K	0.2463	likely_benign	0.1992	benign	0.108	Stabilizing	0.124	N	0.525	neutral	N	0.519057592	None	None	N
N/L	0.3417	ambiguous	0.2812	benign	0.111	Stabilizing	0.567	D	0.627	neutral	None	None	None	None	N
N/M	0.3735	ambiguous	0.3077	benign	0.321	Stabilizing	0.968	D	0.663	neutral	None	None	None	None	N
N/P	0.8155	likely_pathogenic	0.7285	pathogenic	0.006	Stabilizing	0.567	D	0.652	neutral	None	None	None	None	N
N/Q	0.2987	likely_benign	0.245	benign	-0.378	Destabilizing	0.567	D	0.482	neutral	None	None	None	None	N
N/R	0.3446	ambiguous	0.2728	benign	0.17	Stabilizing	0.567	D	0.489	neutral	None	None	None	None	N
N/S	0.1148	likely_benign	0.0951	benign	-0.187	Destabilizing	0.001	N	0.342	neutral	N	0.517017364	None	None	N
N/T	0.1824	likely_benign	0.1487	benign	-0.063	Destabilizing	0.124	N	0.521	neutral	N	0.481839717	None	None	N
N/V	0.389	ambiguous	0.2985	benign	0.006	Stabilizing	0.567	D	0.668	neutral	None	None	None	None	N
N/W	0.7806	likely_pathogenic	0.6896	pathogenic	-0.572	Destabilizing	0.968	D	0.739	prob.delet.	None	None	None	None	N
N/Y	0.1845	likely_benign	0.1516	benign	-0.304	Destabilizing	0.667	D	0.656	neutral	N	0.511515544	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.