TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24103	72532;72533;72534	chr2:178573825;178573824;178573823	chr2:179438552;179438551;179438550
N2AB	22462	67609;67610;67611	chr2:178573825;178573824;178573823	chr2:179438552;179438551;179438550
N2A	21535	64828;64829;64830	chr2:178573825;178573824;178573823	chr2:179438552;179438551;179438550
N2B	15038	45337;45338;45339	chr2:178573825;178573824;178573823	chr2:179438552;179438551;179438550
Novex-1	15163	45712;45713;45714	chr2:178573825;178573824;178573823	chr2:179438552;179438551;179438550
Novex-2	15230	45913;45914;45915	chr2:178573825;178573824;178573823	chr2:179438552;179438551;179438550
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-131
• Domain position: 75
• Structural Position: 157
• Q(SASA): 0.1808
• 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
T/I	rs758801815	0.087	0.993	D	0.791	0.438	0.53911333632	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
T/I	rs758801815	0.087	0.993	D	0.791	0.438	0.53911333632	gnomAD-4.0.0	1.36996E-06	None	None	None	None	N	None	2.99294E-05	0	None	0	0	None	0	0	9.00328E-07	0	0
T/R	None	None	0.997	N	0.805	0.469	0.664903063441	gnomAD-4.0.0	6.84978E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16198E-05	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
T/A	0.1149	likely_benign	0.1377	benign	-1.053	Destabilizing	0.117	N	0.389	neutral	N	0.50910341	None	None	N
T/C	0.3866	ambiguous	0.4826	ambiguous	-1.05	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
T/D	0.6613	likely_pathogenic	0.7242	pathogenic	-1.398	Destabilizing	0.998	D	0.79	deleterious	None	None	None	None	N
T/E	0.3795	ambiguous	0.4413	ambiguous	-1.308	Destabilizing	0.995	D	0.76	deleterious	None	None	None	None	N
T/F	0.225	likely_benign	0.2968	benign	-0.912	Destabilizing	0.998	D	0.85	deleterious	None	None	None	None	N
T/G	0.4623	ambiguous	0.5239	ambiguous	-1.379	Destabilizing	0.966	D	0.689	prob.neutral	None	None	None	None	N
T/H	0.2267	likely_benign	0.275	benign	-1.58	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
T/I	0.1221	likely_benign	0.166	benign	-0.245	Destabilizing	0.993	D	0.791	deleterious	D	0.530192597	None	None	N
T/K	0.1772	likely_benign	0.2222	benign	-0.921	Destabilizing	0.993	D	0.755	deleterious	N	0.49517316	None	None	N
T/L	0.0899	likely_benign	0.1102	benign	-0.245	Destabilizing	0.983	D	0.646	neutral	None	None	None	None	N
T/M	0.0804	likely_benign	0.0899	benign	-0.11	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
T/N	0.2162	likely_benign	0.2653	benign	-1.262	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
T/P	0.8501	likely_pathogenic	0.8368	pathogenic	-0.482	Destabilizing	0.997	D	0.811	deleterious	D	0.546668273	None	None	N
T/Q	0.2121	likely_benign	0.2423	benign	-1.344	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
T/R	0.1466	likely_benign	0.1799	benign	-0.778	Destabilizing	0.997	D	0.805	deleterious	N	0.512452199	None	None	N
T/S	0.1669	likely_benign	0.1952	benign	-1.459	Destabilizing	0.955	D	0.571	neutral	N	0.483757453	None	None	N
T/V	0.1102	likely_benign	0.1432	benign	-0.482	Destabilizing	0.966	D	0.56	neutral	None	None	None	None	N
T/W	0.5357	ambiguous	0.5893	pathogenic	-0.915	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
T/Y	0.2555	likely_benign	0.3107	benign	-0.615	Destabilizing	0.999	D	0.843	deleterious	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.