TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28163	84712;84713;84714	chr2:178561645;178561644;178561643	chr2:179426372;179426371;179426370
N2AB	26522	79789;79790;79791	chr2:178561645;178561644;178561643	chr2:179426372;179426371;179426370
N2A	25595	77008;77009;77010	chr2:178561645;178561644;178561643	chr2:179426372;179426371;179426370
N2B	19098	57517;57518;57519	chr2:178561645;178561644;178561643	chr2:179426372;179426371;179426370
Novex-1	19223	57892;57893;57894	chr2:178561645;178561644;178561643	chr2:179426372;179426371;179426370
Novex-2	19290	58093;58094;58095	chr2:178561645;178561644;178561643	chr2:179426372;179426371;179426370
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-93
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.2751
• 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
V/A	None	None	0.999	N	0.621	0.396	0.628378350306	gnomAD-4.0.0	3.20099E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.74749E-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
V/A	0.4049	ambiguous	0.3817	ambiguous	-1.592	Destabilizing	0.999	D	0.621	neutral	N	0.50430157	None	None	N
V/C	0.9393	likely_pathogenic	0.9313	pathogenic	-0.945	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/D	0.9783	likely_pathogenic	0.9717	pathogenic	-1.641	Destabilizing	1.0	D	0.885	deleterious	N	0.508522936	None	None	N
V/E	0.9581	likely_pathogenic	0.9463	pathogenic	-1.567	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
V/F	0.8225	likely_pathogenic	0.7814	pathogenic	-1.079	Destabilizing	1.0	D	0.867	deleterious	N	0.487083637	None	None	N
V/G	0.744	likely_pathogenic	0.7158	pathogenic	-1.984	Destabilizing	1.0	D	0.869	deleterious	N	0.503888127	None	None	N
V/H	0.9878	likely_pathogenic	0.9845	pathogenic	-1.57	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
V/I	0.1063	likely_benign	0.0989	benign	-0.579	Destabilizing	0.997	D	0.599	neutral	N	0.45997479	None	None	N
V/K	0.9769	likely_pathogenic	0.97	pathogenic	-1.377	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/L	0.6781	likely_pathogenic	0.5984	pathogenic	-0.579	Destabilizing	0.997	D	0.615	neutral	N	0.52075389	None	None	N
V/M	0.5809	likely_pathogenic	0.544	ambiguous	-0.411	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
V/N	0.9237	likely_pathogenic	0.9005	pathogenic	-1.284	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
V/P	0.7943	likely_pathogenic	0.7456	pathogenic	-0.883	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/Q	0.9628	likely_pathogenic	0.9531	pathogenic	-1.346	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/R	0.9612	likely_pathogenic	0.9493	pathogenic	-0.953	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/S	0.783	likely_pathogenic	0.7494	pathogenic	-1.814	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
V/T	0.512	ambiguous	0.4844	ambiguous	-1.619	Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	N
V/W	0.9928	likely_pathogenic	0.9903	pathogenic	-1.4	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/Y	0.9705	likely_pathogenic	0.9604	pathogenic	-1.058	Destabilizing	1.0	D	0.867	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.