TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32366	97321;97322;97323	chr2:178542758;178542757;178542756	chr2:179407485;179407484;179407483
N2AB	30725	92398;92399;92400	chr2:178542758;178542757;178542756	chr2:179407485;179407484;179407483
N2A	29798	89617;89618;89619	chr2:178542758;178542757;178542756	chr2:179407485;179407484;179407483
N2B	23301	70126;70127;70128	chr2:178542758;178542757;178542756	chr2:179407485;179407484;179407483
Novex-1	23426	70501;70502;70503	chr2:178542758;178542757;178542756	chr2:179407485;179407484;179407483
Novex-2	23493	70702;70703;70704	chr2:178542758;178542757;178542756	chr2:179407485;179407484;179407483
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-154
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.1127
• 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
I/S	rs1695213145	None	0.991	D	0.828	0.885	0.938880340865	gnomAD-4.0.0	1.59121E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85824E-06	0	0
I/V	rs1304811622	-1.848	0.02	D	0.259	0.354	0.538792235971	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	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
I/A	0.9212	likely_pathogenic	0.8995	pathogenic	-2.741	Highly Destabilizing	0.91	D	0.71	prob.delet.	None	None	None	None	N
I/C	0.9296	likely_pathogenic	0.9156	pathogenic	-2.264	Highly Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
I/D	0.9967	likely_pathogenic	0.9958	pathogenic	-3.135	Highly Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
I/E	0.9892	likely_pathogenic	0.9855	pathogenic	-2.957	Highly Destabilizing	0.993	D	0.856	deleterious	None	None	None	None	N
I/F	0.4408	ambiguous	0.4223	ambiguous	-1.728	Destabilizing	0.991	D	0.735	prob.delet.	D	0.559255628	None	None	N
I/G	0.9865	likely_pathogenic	0.9817	pathogenic	-3.253	Highly Destabilizing	0.993	D	0.85	deleterious	None	None	None	None	N
I/H	0.9712	likely_pathogenic	0.9646	pathogenic	-2.582	Highly Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
I/K	0.9704	likely_pathogenic	0.965	pathogenic	-2.261	Highly Destabilizing	0.993	D	0.854	deleterious	None	None	None	None	N
I/L	0.1996	likely_benign	0.1862	benign	-1.278	Destabilizing	0.58	D	0.445	neutral	D	0.54634444	None	None	N
I/M	0.2554	likely_benign	0.2365	benign	-1.266	Destabilizing	0.991	D	0.699	prob.neutral	D	0.566513453	None	None	N
I/N	0.9552	likely_pathogenic	0.9469	pathogenic	-2.524	Highly Destabilizing	0.997	D	0.857	deleterious	D	0.589285231	None	None	N
I/P	0.9936	likely_pathogenic	0.9929	pathogenic	-1.745	Destabilizing	0.998	D	0.853	deleterious	None	None	None	None	N
I/Q	0.9689	likely_pathogenic	0.9623	pathogenic	-2.481	Highly Destabilizing	0.998	D	0.871	deleterious	None	None	None	None	N
I/R	0.9539	likely_pathogenic	0.947	pathogenic	-1.782	Destabilizing	0.993	D	0.864	deleterious	None	None	None	None	N
I/S	0.9447	likely_pathogenic	0.9308	pathogenic	-3.214	Highly Destabilizing	0.991	D	0.828	deleterious	D	0.605304592	None	None	N
I/T	0.9321	likely_pathogenic	0.9177	pathogenic	-2.897	Highly Destabilizing	0.939	D	0.748	deleterious	D	0.604900984	None	None	N
I/V	0.1056	likely_benign	0.0932	benign	-1.745	Destabilizing	0.02	N	0.259	neutral	D	0.579546977	None	None	N
I/W	0.9633	likely_pathogenic	0.9605	pathogenic	-2.066	Highly Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
I/Y	0.9046	likely_pathogenic	0.9022	pathogenic	-1.831	Destabilizing	0.998	D	0.758	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.