TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31233	93922;93923;93924	chr2:178547929;178547928;178547927	chr2:179412656;179412655;179412654
N2AB	29592	88999;89000;89001	chr2:178547929;178547928;178547927	chr2:179412656;179412655;179412654
N2A	28665	86218;86219;86220	chr2:178547929;178547928;178547927	chr2:179412656;179412655;179412654
N2B	22168	66727;66728;66729	chr2:178547929;178547928;178547927	chr2:179412656;179412655;179412654
Novex-1	22293	67102;67103;67104	chr2:178547929;178547928;178547927	chr2:179412656;179412655;179412654
Novex-2	22360	67303;67304;67305	chr2:178547929;178547928;178547927	chr2:179412656;179412655;179412654
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-151
• Domain position: 16
• Structural Position: 28
• Q(SASA): 0.2848
• 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
F/L	None	None	0.999	N	0.599	0.429	0.176091768786	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	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
F/A	0.9581	likely_pathogenic	0.9667	pathogenic	-2.688	Highly Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
F/C	0.7479	likely_pathogenic	0.7775	pathogenic	-1.974	Destabilizing	1.0	D	0.807	deleterious	N	0.45617264	None	None	I
F/D	0.9967	likely_pathogenic	0.9974	pathogenic	-3.261	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
F/E	0.9951	likely_pathogenic	0.9959	pathogenic	-3.027	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
F/G	0.9892	likely_pathogenic	0.9916	pathogenic	-3.17	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
F/H	0.9752	likely_pathogenic	0.9778	pathogenic	-1.94	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
F/I	0.3438	ambiguous	0.3467	ambiguous	-1.114	Destabilizing	1.0	D	0.763	deleterious	N	0.40395007	None	None	I
F/K	0.9952	likely_pathogenic	0.9956	pathogenic	-2.153	Highly Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
F/L	0.9118	likely_pathogenic	0.9101	pathogenic	-1.114	Destabilizing	0.999	D	0.599	neutral	N	0.420071528	None	None	I
F/M	0.7339	likely_pathogenic	0.7413	pathogenic	-1.005	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
F/N	0.9905	likely_pathogenic	0.992	pathogenic	-2.728	Highly Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
F/P	0.999	likely_pathogenic	0.9991	pathogenic	-1.652	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
F/Q	0.9895	likely_pathogenic	0.9908	pathogenic	-2.593	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
F/R	0.9888	likely_pathogenic	0.9896	pathogenic	-1.82	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
F/S	0.9752	likely_pathogenic	0.9795	pathogenic	-3.349	Highly Destabilizing	1.0	D	0.797	deleterious	N	0.4626671	None	None	I
F/T	0.9656	likely_pathogenic	0.9698	pathogenic	-2.988	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
F/V	0.3877	ambiguous	0.4056	ambiguous	-1.652	Destabilizing	1.0	D	0.757	deleterious	N	0.440713373	None	None	I
F/W	0.8854	likely_pathogenic	0.898	pathogenic	-0.302	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
F/Y	0.6324	likely_pathogenic	0.6449	pathogenic	-0.699	Destabilizing	0.999	D	0.607	neutral	N	0.474023405	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.