TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29953	90082;90083;90084	chr2:178553043;178553042;178553041	chr2:179417770;179417769;179417768
N2AB	28312	85159;85160;85161	chr2:178553043;178553042;178553041	chr2:179417770;179417769;179417768
N2A	27385	82378;82379;82380	chr2:178553043;178553042;178553041	chr2:179417770;179417769;179417768
N2B	20888	62887;62888;62889	chr2:178553043;178553042;178553041	chr2:179417770;179417769;179417768
Novex-1	21013	63262;63263;63264	chr2:178553043;178553042;178553041	chr2:179417770;179417769;179417768
Novex-2	21080	63463;63464;63465	chr2:178553043;178553042;178553041	chr2:179417770;179417769;179417768
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-106
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.2324
• 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
L/F	None	None	None	N	0.156	0.098	0.28492961333	gnomAD-4.0.0	3.19124E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71781E-06	0	0
L/I	None	None	0.004	N	0.323	0.06	0.281780670237	gnomAD-4.0.0	1.59562E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85891E-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
L/A	0.1248	likely_benign	0.1361	benign	-2.119	Highly Destabilizing	0.007	N	0.334	neutral	None	None	None	None	N
L/C	0.2303	likely_benign	0.2229	benign	-1.323	Destabilizing	0.628	D	0.5	neutral	None	None	None	None	N
L/D	0.4884	ambiguous	0.4914	ambiguous	-1.842	Destabilizing	0.072	N	0.509	neutral	None	None	None	None	N
L/E	0.277	likely_benign	0.2799	benign	-1.736	Destabilizing	0.072	N	0.465	neutral	None	None	None	None	N
L/F	0.0671	likely_benign	0.0641	benign	-1.334	Destabilizing	None	N	0.156	neutral	N	0.444522548	None	None	N
L/G	0.3277	likely_benign	0.3355	benign	-2.555	Highly Destabilizing	0.072	N	0.419	neutral	None	None	None	None	N
L/H	0.106	likely_benign	0.105	benign	-1.875	Destabilizing	0.295	N	0.549	neutral	N	0.415815794	None	None	N
L/I	0.0637	likely_benign	0.0619	benign	-0.926	Destabilizing	0.004	N	0.323	neutral	N	0.463108309	None	None	N
L/K	0.2596	likely_benign	0.2566	benign	-1.407	Destabilizing	0.072	N	0.453	neutral	None	None	None	None	N
L/M	0.0748	likely_benign	0.0758	benign	-0.774	Destabilizing	0.356	N	0.456	neutral	None	None	None	None	N
L/N	0.1711	likely_benign	0.1781	benign	-1.392	Destabilizing	0.072	N	0.536	neutral	None	None	None	None	N
L/P	0.9013	likely_pathogenic	0.9012	pathogenic	-1.298	Destabilizing	0.295	N	0.582	neutral	N	0.511323543	None	None	N
L/Q	0.0936	likely_benign	0.096	benign	-1.447	Destabilizing	0.356	N	0.571	neutral	None	None	None	None	N
L/R	0.1825	likely_benign	0.1751	benign	-0.966	Destabilizing	0.295	N	0.579	neutral	N	0.419373387	None	None	N
L/S	0.1042	likely_benign	0.1116	benign	-2.098	Highly Destabilizing	0.001	N	0.349	neutral	None	None	None	None	N
L/T	0.0922	likely_benign	0.0957	benign	-1.866	Destabilizing	None	N	0.238	neutral	None	None	None	None	N
L/V	0.0661	likely_benign	0.0666	benign	-1.298	Destabilizing	None	N	0.13	neutral	N	0.411756768	None	None	N
L/W	0.1631	likely_benign	0.1535	benign	-1.563	Destabilizing	0.676	D	0.548	neutral	None	None	None	None	N
L/Y	0.1775	likely_benign	0.1685	benign	-1.303	Destabilizing	0.038	N	0.479	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.