TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2797	8614;8615;8616	chr2:178770312;178770311;178770310	chr2:179635039;179635038;179635037
N2AB	2797	8614;8615;8616	chr2:178770312;178770311;178770310	chr2:179635039;179635038;179635037
N2A	2797	8614;8615;8616	chr2:178770312;178770311;178770310	chr2:179635039;179635038;179635037
N2B	2751	8476;8477;8478	chr2:178770312;178770311;178770310	chr2:179635039;179635038;179635037
Novex-1	2751	8476;8477;8478	chr2:178770312;178770311;178770310	chr2:179635039;179635038;179635037
Novex-2	2751	8476;8477;8478	chr2:178770312;178770311;178770310	chr2:179635039;179635038;179635037
Novex-3	2797	8614;8615;8616	chr2:178770312;178770311;178770310	chr2:179635039;179635038;179635037

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-18
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1894
• 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	rs1561222466	None	0.998	D	0.85	0.777	0.912926368446	gnomAD-4.0.0	6.84065E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99289E-07	0	0
I/T	rs1561222466	None	0.989	D	0.775	0.761	0.800972959348	gnomAD-4.0.0	6.84065E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99289E-07	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
I/A	0.9767	likely_pathogenic	0.9759	pathogenic	-1.908	Destabilizing	0.992	D	0.683	prob.neutral	None	None	None	None	N
I/C	0.9762	likely_pathogenic	0.9814	pathogenic	-1.161	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
I/D	0.9966	likely_pathogenic	0.9964	pathogenic	-1.505	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/E	0.9933	likely_pathogenic	0.9924	pathogenic	-1.408	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/F	0.5162	ambiguous	0.5394	ambiguous	-1.09	Destabilizing	0.998	D	0.739	prob.delet.	N	0.491420688	None	None	N
I/G	0.9939	likely_pathogenic	0.9945	pathogenic	-2.334	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
I/H	0.9892	likely_pathogenic	0.9902	pathogenic	-1.638	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
I/K	0.9855	likely_pathogenic	0.9852	pathogenic	-1.452	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/L	0.4207	ambiguous	0.4122	ambiguous	-0.76	Destabilizing	0.889	D	0.544	neutral	N	0.511633454	None	None	N
I/M	0.312	likely_benign	0.317	benign	-0.619	Destabilizing	0.998	D	0.719	prob.delet.	D	0.686107141	None	None	N
I/N	0.9502	likely_pathogenic	0.9517	pathogenic	-1.41	Destabilizing	0.999	D	0.881	deleterious	D	0.689192799	None	None	N
I/P	0.9844	likely_pathogenic	0.9813	pathogenic	-1.114	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
I/Q	0.9877	likely_pathogenic	0.9876	pathogenic	-1.447	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
I/R	0.9795	likely_pathogenic	0.9809	pathogenic	-0.996	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
I/S	0.9785	likely_pathogenic	0.9798	pathogenic	-2.088	Highly Destabilizing	0.998	D	0.85	deleterious	D	0.688377276	None	None	N
I/T	0.9714	likely_pathogenic	0.971	pathogenic	-1.867	Destabilizing	0.989	D	0.775	deleterious	D	0.687915137	None	None	N
I/V	0.2176	likely_benign	0.208	benign	-1.114	Destabilizing	0.333	N	0.273	neutral	D	0.55238514	None	None	N
I/W	0.972	likely_pathogenic	0.9767	pathogenic	-1.308	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
I/Y	0.9177	likely_pathogenic	0.9292	pathogenic	-1.052	Destabilizing	1.0	D	0.772	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.