TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10025	30298;30299;30300	chr2:178704297;178704296;178704295	chr2:179569024;179569023;179569022
N2AB	9708	29347;29348;29349	chr2:178704297;178704296;178704295	chr2:179569024;179569023;179569022
N2A	8781	26566;26567;26568	chr2:178704297;178704296;178704295	chr2:179569024;179569023;179569022
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-85
• Domain position: 37
• Structural Position: 52
• Q(SASA): 0.5278
• 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
G/S	None	None	0.991	None	0.539	0.49	0.267299060538	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
G/V	None	None	1.0	None	0.739	0.573	0.876304189171	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
G/A	0.626	likely_pathogenic	0.761	pathogenic	-0.281	Destabilizing	0.998	D	0.48	neutral	None	None	None	None	N
G/C	0.7545	likely_pathogenic	0.8728	pathogenic	-0.866	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
G/D	0.3529	ambiguous	0.5077	ambiguous	-0.395	Destabilizing	1.0	D	0.632	neutral	None	None	None	None	N
G/E	0.4705	ambiguous	0.6557	pathogenic	-0.532	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
G/F	0.9641	likely_pathogenic	0.9826	pathogenic	-0.86	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
G/H	0.6407	likely_pathogenic	0.7812	pathogenic	-0.491	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
G/I	0.9449	likely_pathogenic	0.9758	pathogenic	-0.323	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
G/K	0.6097	likely_pathogenic	0.7337	pathogenic	-0.827	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
G/L	0.9416	likely_pathogenic	0.9704	pathogenic	-0.323	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
G/M	0.9453	likely_pathogenic	0.9742	pathogenic	-0.498	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
G/N	0.4119	ambiguous	0.5709	pathogenic	-0.495	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
G/P	0.9975	likely_pathogenic	0.9987	pathogenic	-0.274	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
G/Q	0.5181	ambiguous	0.6675	pathogenic	-0.725	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
G/R	0.4655	ambiguous	0.6117	pathogenic	-0.416	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
G/S	0.2136	likely_benign	0.3193	benign	-0.687	Destabilizing	0.991	D	0.539	neutral	None	None	None	None	N
G/T	0.742	likely_pathogenic	0.8534	pathogenic	-0.743	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
G/V	0.9112	likely_pathogenic	0.9601	pathogenic	-0.274	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
G/W	0.8754	likely_pathogenic	0.9325	pathogenic	-1.05	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
G/Y	0.8857	likely_pathogenic	0.9418	pathogenic	-0.688	Destabilizing	1.0	D	0.762	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.