TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22091	66496;66497;66498	chr2:178582098;178582097;178582096	chr2:179446825;179446824;179446823
N2AB	20450	61573;61574;61575	chr2:178582098;178582097;178582096	chr2:179446825;179446824;179446823
N2A	19523	58792;58793;58794	chr2:178582098;178582097;178582096	chr2:179446825;179446824;179446823
N2B	13026	39301;39302;39303	chr2:178582098;178582097;178582096	chr2:179446825;179446824;179446823
Novex-1	13151	39676;39677;39678	chr2:178582098;178582097;178582096	chr2:179446825;179446824;179446823
Novex-2	13218	39877;39878;39879	chr2:178582098;178582097;178582096	chr2:179446825;179446824;179446823
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-48
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.349
• 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
L/S	None	None	0.939	N	0.622	0.382	0.488055169367	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
L/A	0.4641	ambiguous	0.4577	ambiguous	-2.508	Highly Destabilizing	0.742	D	0.507	neutral	None	None	None	None	N
L/C	0.5248	ambiguous	0.5005	ambiguous	-1.936	Destabilizing	0.996	D	0.592	neutral	None	None	None	None	N
L/D	0.8796	likely_pathogenic	0.8702	pathogenic	-2.727	Highly Destabilizing	0.984	D	0.664	neutral	None	None	None	None	N
L/E	0.61	likely_pathogenic	0.6285	pathogenic	-2.557	Highly Destabilizing	0.953	D	0.659	neutral	None	None	None	None	N
L/F	0.1096	likely_benign	0.1032	benign	-1.485	Destabilizing	0.521	D	0.511	neutral	N	0.474690739	None	None	N
L/G	0.8245	likely_pathogenic	0.818	pathogenic	-2.991	Highly Destabilizing	0.953	D	0.655	neutral	None	None	None	None	N
L/H	0.2726	likely_benign	0.2567	benign	-2.319	Highly Destabilizing	0.974	D	0.667	neutral	None	None	None	None	N
L/I	0.0747	likely_benign	0.0791	benign	-1.137	Destabilizing	0.009	N	0.283	neutral	None	None	None	None	N
L/K	0.6225	likely_pathogenic	0.6484	pathogenic	-1.888	Destabilizing	0.953	D	0.634	neutral	None	None	None	None	N
L/M	0.1032	likely_benign	0.1035	benign	-1.202	Destabilizing	0.078	N	0.433	neutral	N	0.481944785	None	None	N
L/N	0.4898	ambiguous	0.5063	ambiguous	-2.091	Highly Destabilizing	0.953	D	0.665	neutral	None	None	None	None	N
L/P	0.988	likely_pathogenic	0.9884	pathogenic	-1.573	Destabilizing	0.984	D	0.665	neutral	None	None	None	None	N
L/Q	0.2671	likely_benign	0.2732	benign	-2.056	Highly Destabilizing	0.953	D	0.645	neutral	None	None	None	None	N
L/R	0.4964	ambiguous	0.4932	ambiguous	-1.492	Destabilizing	0.953	D	0.633	neutral	None	None	None	None	N
L/S	0.4563	ambiguous	0.4376	ambiguous	-2.773	Highly Destabilizing	0.939	D	0.622	neutral	N	0.47718954	None	None	N
L/T	0.3157	likely_benign	0.3133	benign	-2.472	Highly Destabilizing	0.742	D	0.551	neutral	None	None	None	None	N
L/V	0.0998	likely_benign	0.103	benign	-1.573	Destabilizing	0.309	N	0.475	neutral	N	0.441578243	None	None	N
L/W	0.2593	likely_benign	0.2324	benign	-1.786	Destabilizing	0.983	D	0.651	neutral	N	0.46686069	None	None	N
L/Y	0.2856	likely_benign	0.2529	benign	-1.543	Destabilizing	0.02	N	0.399	neutral	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.