TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14039	42340;42341;42342	chr2:178634759;178634758;178634757	chr2:179499486;179499485;179499484
N2AB	12398	37417;37418;37419	chr2:178634759;178634758;178634757	chr2:179499486;179499485;179499484
N2A	11471	34636;34637;34638	chr2:178634759;178634758;178634757	chr2:179499486;179499485;179499484
N2B	4974	15145;15146;15147	chr2:178634759;178634758;178634757	chr2:179499486;179499485;179499484
Novex-1	5099	15520;15521;15522	chr2:178634759;178634758;178634757	chr2:179499486;179499485;179499484
Novex-2	5166	15721;15722;15723	chr2:178634759;178634758;178634757	chr2:179499486;179499485;179499484
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-90
• Domain position: 75
• Structural Position: 159
• Q(SASA): 0.6511
• Predicted PPI site: I

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	0.001	N	0.397	0.057	0.170165803431	gnomAD-4.0.0	2.73785E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69921E-06	1.16007E-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
L/A	0.4407	ambiguous	0.324	benign	-0.809	Destabilizing	0.08	N	0.513	neutral	None	None	None	None	I
L/C	0.4777	ambiguous	0.4847	ambiguous	-0.701	Destabilizing	0.003	N	0.478	neutral	None	None	None	None	I
L/D	0.8685	likely_pathogenic	0.7732	pathogenic	-0.514	Destabilizing	0.552	D	0.783	deleterious	None	None	None	None	I
L/E	0.6231	likely_pathogenic	0.4869	ambiguous	-0.584	Destabilizing	0.552	D	0.759	deleterious	None	None	None	None	I
L/F	0.2442	likely_benign	0.1614	benign	-0.743	Destabilizing	0.001	N	0.397	neutral	N	0.437061855	None	None	I
L/G	0.5912	likely_pathogenic	0.5065	ambiguous	-0.999	Destabilizing	0.378	N	0.74	deleterious	None	None	None	None	I
L/H	0.5654	likely_pathogenic	0.4043	ambiguous	-0.225	Destabilizing	0.914	D	0.776	deleterious	N	0.419177713	None	None	I
L/I	0.2817	likely_benign	0.1887	benign	-0.412	Destabilizing	0.061	N	0.436	neutral	N	0.417278044	None	None	I
L/K	0.5606	ambiguous	0.4357	ambiguous	-0.545	Destabilizing	0.378	N	0.694	prob.delet.	None	None	None	None	I
L/M	0.1978	likely_benign	0.1433	benign	-0.511	Destabilizing	0.012	N	0.421	neutral	None	None	None	None	I
L/N	0.5881	likely_pathogenic	0.4493	ambiguous	-0.373	Destabilizing	0.552	D	0.786	deleterious	None	None	None	None	I
L/P	0.8589	likely_pathogenic	0.7038	pathogenic	-0.512	Destabilizing	0.739	D	0.783	deleterious	N	0.419687232	None	None	I
L/Q	0.3699	ambiguous	0.2327	benign	-0.579	Destabilizing	0.378	N	0.723	deleterious	None	None	None	None	I
L/R	0.5183	ambiguous	0.3847	ambiguous	0.037	Stabilizing	0.314	N	0.711	prob.delet.	N	0.435468575	None	None	I
L/S	0.5717	likely_pathogenic	0.3984	ambiguous	-0.802	Destabilizing	0.378	N	0.511	neutral	None	None	None	None	I
L/T	0.5321	ambiguous	0.3983	ambiguous	-0.759	Destabilizing	0.378	N	0.437	neutral	None	None	None	None	I
L/V	0.2662	likely_benign	0.1846	benign	-0.512	Destabilizing	0.061	N	0.477	neutral	N	0.431222318	None	None	I
L/W	0.5593	ambiguous	0.4243	ambiguous	-0.77	Destabilizing	0.823	D	0.775	deleterious	None	None	None	None	I
L/Y	0.5328	ambiguous	0.4218	ambiguous	-0.53	Destabilizing	0.233	N	0.489	neutral	None	None	None	None	I

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.