TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21774	65545;65546;65547	chr2:178583862;178583861;178583860	chr2:179448589;179448588;179448587
N2AB	20133	60622;60623;60624	chr2:178583862;178583861;178583860	chr2:179448589;179448588;179448587
N2A	19206	57841;57842;57843	chr2:178583862;178583861;178583860	chr2:179448589;179448588;179448587
N2B	12709	38350;38351;38352	chr2:178583862;178583861;178583860	chr2:179448589;179448588;179448587
Novex-1	12834	38725;38726;38727	chr2:178583862;178583861;178583860	chr2:179448589;179448588;179448587
Novex-2	12901	38926;38927;38928	chr2:178583862;178583861;178583860	chr2:179448589;179448588;179448587
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-46
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0647
• 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	0.001	N	0.319	0.112	0.32580497728	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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	0.1908	likely_benign	0.2769	benign	-2.197	Highly Destabilizing	0.001	N	0.319	neutral	N	0.470687676	None	None	N
V/C	0.8267	likely_pathogenic	0.8632	pathogenic	-2.299	Highly Destabilizing	0.947	D	0.763	deleterious	None	None	None	None	N
V/D	0.9941	likely_pathogenic	0.9967	pathogenic	-2.965	Highly Destabilizing	0.7	D	0.859	deleterious	None	None	None	None	N
V/E	0.9854	likely_pathogenic	0.9906	pathogenic	-2.695	Highly Destabilizing	0.638	D	0.836	deleterious	D	0.525675685	None	None	N
V/F	0.8904	likely_pathogenic	0.8901	pathogenic	-1.366	Destabilizing	0.826	D	0.806	deleterious	None	None	None	None	N
V/G	0.6946	likely_pathogenic	0.7846	pathogenic	-2.785	Highly Destabilizing	0.201	N	0.812	deleterious	D	0.537196575	None	None	N
V/H	0.9959	likely_pathogenic	0.9969	pathogenic	-2.638	Highly Destabilizing	0.982	D	0.824	deleterious	None	None	None	None	N
V/I	0.1561	likely_benign	0.1325	benign	-0.525	Destabilizing	0.172	N	0.511	neutral	N	0.510627323	None	None	N
V/K	0.9906	likely_pathogenic	0.9931	pathogenic	-1.825	Destabilizing	0.7	D	0.84	deleterious	None	None	None	None	N
V/L	0.641	likely_pathogenic	0.6256	pathogenic	-0.525	Destabilizing	0.094	N	0.618	neutral	N	0.511283471	None	None	N
V/M	0.6812	likely_pathogenic	0.6634	pathogenic	-0.956	Destabilizing	0.826	D	0.715	prob.delet.	None	None	None	None	N
V/N	0.9789	likely_pathogenic	0.9873	pathogenic	-2.359	Highly Destabilizing	0.826	D	0.852	deleterious	None	None	None	None	N
V/P	0.9864	likely_pathogenic	0.9937	pathogenic	-1.058	Destabilizing	0.7	D	0.853	deleterious	None	None	None	None	N
V/Q	0.9794	likely_pathogenic	0.9858	pathogenic	-2.1	Highly Destabilizing	0.826	D	0.841	deleterious	None	None	None	None	N
V/R	0.9728	likely_pathogenic	0.9816	pathogenic	-1.815	Destabilizing	0.7	D	0.853	deleterious	None	None	None	None	N
V/S	0.7334	likely_pathogenic	0.8302	pathogenic	-3.005	Highly Destabilizing	0.25	N	0.815	deleterious	None	None	None	None	N
V/T	0.5636	ambiguous	0.6668	pathogenic	-2.566	Highly Destabilizing	0.25	N	0.705	prob.neutral	None	None	None	None	N
V/W	0.9985	likely_pathogenic	0.9986	pathogenic	-1.869	Destabilizing	0.982	D	0.798	deleterious	None	None	None	None	N
V/Y	0.9873	likely_pathogenic	0.9893	pathogenic	-1.503	Destabilizing	0.826	D	0.805	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.