TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2507	7744;7745;7746	chr2:178773537;178773536;178773535	chr2:179638264;179638263;179638262
N2AB	2507	7744;7745;7746	chr2:178773537;178773536;178773535	chr2:179638264;179638263;179638262
N2A	2507	7744;7745;7746	chr2:178773537;178773536;178773535	chr2:179638264;179638263;179638262
N2B	2461	7606;7607;7608	chr2:178773537;178773536;178773535	chr2:179638264;179638263;179638262
Novex-1	2461	7606;7607;7608	chr2:178773537;178773536;178773535	chr2:179638264;179638263;179638262
Novex-2	2461	7606;7607;7608	chr2:178773537;178773536;178773535	chr2:179638264;179638263;179638262
Novex-3	2507	7744;7745;7746	chr2:178773537;178773536;178773535	chr2:179638264;179638263;179638262

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-14
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.0984
• 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	rs1280887940	None	0.999	N	0.772	0.478	0.5632085275	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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
T/A	0.1358	likely_benign	0.1232	benign	-0.787	Destabilizing	0.962	D	0.513	neutral	N	0.439394171	None	None	N
T/C	0.4722	ambiguous	0.4262	ambiguous	-1.188	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
T/D	0.9755	likely_pathogenic	0.9651	pathogenic	-2.614	Highly Destabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	N
T/E	0.9713	likely_pathogenic	0.9596	pathogenic	-2.452	Highly Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
T/F	0.903	likely_pathogenic	0.878	pathogenic	-0.649	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
T/G	0.6388	likely_pathogenic	0.5877	pathogenic	-1.108	Destabilizing	0.994	D	0.655	neutral	None	None	None	None	N
T/H	0.9474	likely_pathogenic	0.9311	pathogenic	-1.315	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
T/I	0.509	ambiguous	0.4626	ambiguous	0.02	Stabilizing	0.999	D	0.772	deleterious	N	0.488019119	None	None	N
T/K	0.9635	likely_pathogenic	0.9525	pathogenic	-0.818	Destabilizing	0.998	D	0.724	prob.delet.	None	None	None	None	N
T/L	0.361	ambiguous	0.3022	benign	0.02	Stabilizing	0.997	D	0.647	neutral	None	None	None	None	N
T/M	0.3096	likely_benign	0.2447	benign	-0.077	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
T/N	0.6982	likely_pathogenic	0.6322	pathogenic	-1.679	Destabilizing	0.998	D	0.741	deleterious	D	0.633121632	None	None	N
T/P	0.5428	ambiguous	0.4979	ambiguous	-0.22	Destabilizing	0.999	D	0.775	deleterious	D	0.538121633	None	None	N
T/Q	0.9346	likely_pathogenic	0.9143	pathogenic	-1.552	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
T/R	0.9439	likely_pathogenic	0.9291	pathogenic	-0.86	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
T/S	0.247	likely_benign	0.2186	benign	-1.593	Destabilizing	0.825	D	0.384	neutral	N	0.510001315	None	None	N
T/V	0.2829	likely_benign	0.2573	benign	-0.22	Destabilizing	0.997	D	0.606	neutral	None	None	None	None	N
T/W	0.9906	likely_pathogenic	0.9872	pathogenic	-1.002	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
T/Y	0.9552	likely_pathogenic	0.94	pathogenic	-0.54	Destabilizing	1.0	D	0.787	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.