TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27657	83194;83195;83196	chr2:178563163;178563162;178563161	chr2:179427890;179427889;179427888
N2AB	26016	78271;78272;78273	chr2:178563163;178563162;178563161	chr2:179427890;179427889;179427888
N2A	25089	75490;75491;75492	chr2:178563163;178563162;178563161	chr2:179427890;179427889;179427888
N2B	18592	55999;56000;56001	chr2:178563163;178563162;178563161	chr2:179427890;179427889;179427888
Novex-1	18717	56374;56375;56376	chr2:178563163;178563162;178563161	chr2:179427890;179427889;179427888
Novex-2	18784	56575;56576;56577	chr2:178563163;178563162;178563161	chr2:179427890;179427889;179427888
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-89
• Domain position: 88
• Structural Position: 120
• Q(SASA): 0.3467
• 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
P/T	None	None	0.961	N	0.459	0.296	0.387042434762	gnomAD-4.0.0	1.59139E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85869E-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
P/A	0.0985	likely_benign	0.0935	benign	-1.24	Destabilizing	0.248	N	0.333	neutral	N	0.470315147	None	None	I
P/C	0.5368	ambiguous	0.5405	ambiguous	-0.735	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
P/D	0.7386	likely_pathogenic	0.7233	pathogenic	-1.235	Destabilizing	0.985	D	0.507	neutral	None	None	None	None	I
P/E	0.574	likely_pathogenic	0.5497	ambiguous	-1.326	Destabilizing	0.97	D	0.459	neutral	None	None	None	None	I
P/F	0.5281	ambiguous	0.5202	ambiguous	-1.26	Destabilizing	0.996	D	0.696	prob.neutral	None	None	None	None	I
P/G	0.4919	ambiguous	0.4673	ambiguous	-1.446	Destabilizing	0.97	D	0.551	neutral	None	None	None	None	I
P/H	0.2759	likely_benign	0.289	benign	-0.971	Destabilizing	0.071	N	0.469	neutral	N	0.467570123	None	None	I
P/I	0.5797	likely_pathogenic	0.5218	ambiguous	-0.809	Destabilizing	0.996	D	0.659	neutral	None	None	None	None	I
P/K	0.6827	likely_pathogenic	0.6518	pathogenic	-1.006	Destabilizing	0.97	D	0.479	neutral	None	None	None	None	I
P/L	0.2995	likely_benign	0.26	benign	-0.809	Destabilizing	0.961	D	0.609	neutral	N	0.519841745	None	None	I
P/M	0.5047	ambiguous	0.467	ambiguous	-0.506	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
P/N	0.6061	likely_pathogenic	0.5826	pathogenic	-0.67	Destabilizing	0.991	D	0.576	neutral	None	None	None	None	I
P/Q	0.4093	ambiguous	0.3864	ambiguous	-0.991	Destabilizing	0.996	D	0.554	neutral	None	None	None	None	I
P/R	0.53	ambiguous	0.4976	ambiguous	-0.346	Destabilizing	0.989	D	0.574	neutral	D	0.532883572	None	None	I
P/S	0.2215	likely_benign	0.2058	benign	-1.045	Destabilizing	0.925	D	0.487	neutral	N	0.482178431	None	None	I
P/T	0.2478	likely_benign	0.2209	benign	-1.048	Destabilizing	0.961	D	0.459	neutral	N	0.489686849	None	None	I
P/V	0.387	ambiguous	0.3462	ambiguous	-0.918	Destabilizing	0.97	D	0.552	neutral	None	None	None	None	I
P/W	0.6978	likely_pathogenic	0.702	pathogenic	-1.328	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
P/Y	0.4954	ambiguous	0.4951	ambiguous	-1.077	Destabilizing	0.991	D	0.651	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.