TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24940	75043;75044;75045	chr2:178571314;178571313;178571312	chr2:179436041;179436040;179436039
N2AB	23299	70120;70121;70122	chr2:178571314;178571313;178571312	chr2:179436041;179436040;179436039
N2A	22372	67339;67340;67341	chr2:178571314;178571313;178571312	chr2:179436041;179436040;179436039
N2B	15875	47848;47849;47850	chr2:178571314;178571313;178571312	chr2:179436041;179436040;179436039
Novex-1	16000	48223;48224;48225	chr2:178571314;178571313;178571312	chr2:179436041;179436040;179436039
Novex-2	16067	48424;48425;48426	chr2:178571314;178571313;178571312	chr2:179436041;179436040;179436039
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-69
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1972
• 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
V/A	None	None	0.296	N	0.667	0.358	0.59385865776	gnomAD-4.0.0	6.84322E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99596E-07	0	0
V/D	rs754897261	-1.773	0.879	N	0.812	0.468	0.803159424316	gnomAD-2.1.1	2.82E-05	None	None	None	None	I	None	0	0	None	0	0	None	2.28788E-04	None	0	0	0
V/D	rs754897261	-1.773	0.879	N	0.812	0.468	0.803159424316	gnomAD-4.0.0	1.09492E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.85503E-04	0
V/I	None	None	0.001	N	0.249	0.071	0.245660935333	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62502E-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	0.8649	likely_pathogenic	0.8685	pathogenic	-1.82	Destabilizing	0.296	N	0.667	neutral	N	0.498186453	None	None	I
V/C	0.9244	likely_pathogenic	0.9304	pathogenic	-1.146	Destabilizing	0.991	D	0.713	prob.delet.	None	None	None	None	I
V/D	0.9759	likely_pathogenic	0.9838	pathogenic	-1.906	Destabilizing	0.879	D	0.812	deleterious	N	0.492653045	None	None	I
V/E	0.9553	likely_pathogenic	0.9641	pathogenic	-1.828	Destabilizing	0.906	D	0.778	deleterious	None	None	None	None	I
V/F	0.7911	likely_pathogenic	0.7988	pathogenic	-1.276	Destabilizing	0.782	D	0.773	deleterious	N	0.502741903	None	None	I
V/G	0.8579	likely_pathogenic	0.8806	pathogenic	-2.228	Highly Destabilizing	0.879	D	0.805	deleterious	N	0.517304666	None	None	I
V/H	0.981	likely_pathogenic	0.986	pathogenic	-1.85	Destabilizing	0.991	D	0.783	deleterious	None	None	None	None	I
V/I	0.068	likely_benign	0.066	benign	-0.755	Destabilizing	0.001	N	0.249	neutral	N	0.366402907	None	None	I
V/K	0.9639	likely_pathogenic	0.9709	pathogenic	-1.528	Destabilizing	0.906	D	0.779	deleterious	None	None	None	None	I
V/L	0.4093	ambiguous	0.3968	ambiguous	-0.755	Destabilizing	0.031	N	0.5	neutral	N	0.499837113	None	None	I
V/M	0.5421	ambiguous	0.5583	ambiguous	-0.524	Destabilizing	0.826	D	0.675	prob.neutral	None	None	None	None	I
V/N	0.8375	likely_pathogenic	0.8988	pathogenic	-1.439	Destabilizing	0.967	D	0.815	deleterious	None	None	None	None	I
V/P	0.8328	likely_pathogenic	0.8462	pathogenic	-1.078	Destabilizing	0.967	D	0.754	deleterious	None	None	None	None	I
V/Q	0.9606	likely_pathogenic	0.9673	pathogenic	-1.51	Destabilizing	0.967	D	0.761	deleterious	None	None	None	None	I
V/R	0.9532	likely_pathogenic	0.9614	pathogenic	-1.082	Destabilizing	0.906	D	0.815	deleterious	None	None	None	None	I
V/S	0.9033	likely_pathogenic	0.9216	pathogenic	-2.004	Highly Destabilizing	0.906	D	0.761	deleterious	None	None	None	None	I
V/T	0.8356	likely_pathogenic	0.8507	pathogenic	-1.808	Destabilizing	0.575	D	0.73	prob.delet.	None	None	None	None	I
V/W	0.9906	likely_pathogenic	0.9912	pathogenic	-1.611	Destabilizing	0.991	D	0.766	deleterious	None	None	None	None	I
V/Y	0.9563	likely_pathogenic	0.961	pathogenic	-1.29	Destabilizing	0.906	D	0.743	deleterious	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.