TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23600	71023;71024;71025	chr2:178575334;178575333;178575332	chr2:179440061;179440060;179440059
N2AB	21959	66100;66101;66102	chr2:178575334;178575333;178575332	chr2:179440061;179440060;179440059
N2A	21032	63319;63320;63321	chr2:178575334;178575333;178575332	chr2:179440061;179440060;179440059
N2B	14535	43828;43829;43830	chr2:178575334;178575333;178575332	chr2:179440061;179440060;179440059
Novex-1	14660	44203;44204;44205	chr2:178575334;178575333;178575332	chr2:179440061;179440060;179440059
Novex-2	14727	44404;44405;44406	chr2:178575334;178575333;178575332	chr2:179440061;179440060;179440059
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-59
• Domain position: 69
• Structural Position: 103
• Q(SASA): 0.27
• 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
E/A	rs1168061388	-0.729	0.945	N	0.531	0.315	0.378847511475	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14811E-04	0	None	0	0	None	0	None	0	0	0
E/A	rs1168061388	-0.729	0.945	N	0.531	0.315	0.378847511475	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/A	rs1168061388	-0.729	0.945	N	0.531	0.315	0.378847511475	gnomAD-4.0.0	6.57488E-06	None	None	None	None	N	None	2.41255E-05	0	None	0	0	None	0	0	0	0	0
E/D	None	None	0.815	N	0.423	0.179	0.358134431457	gnomAD-4.0.0	1.59193E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85919E-06	0	0
E/G	None	None	0.998	N	0.695	0.404	0.424313518543	gnomAD-4.0.0	2.40067E-06	None	None	None	None	N	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
E/A	0.2214	likely_benign	0.2126	benign	-0.666	Destabilizing	0.945	D	0.531	neutral	N	0.475865463	None	None	N
E/C	0.9305	likely_pathogenic	0.9232	pathogenic	-0.374	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/D	0.4354	ambiguous	0.4085	ambiguous	-1.119	Destabilizing	0.815	D	0.423	neutral	N	0.478485582	None	None	N
E/F	0.9138	likely_pathogenic	0.9023	pathogenic	0.167	Stabilizing	0.998	D	0.818	deleterious	None	None	None	None	N
E/G	0.4415	ambiguous	0.3981	ambiguous	-1.103	Destabilizing	0.998	D	0.695	prob.neutral	N	0.488640573	None	None	N
E/H	0.8216	likely_pathogenic	0.8032	pathogenic	-0.142	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/I	0.4531	ambiguous	0.4169	ambiguous	0.547	Stabilizing	0.993	D	0.819	deleterious	None	None	None	None	N
E/K	0.4797	ambiguous	0.4346	ambiguous	-0.589	Destabilizing	0.984	D	0.485	neutral	N	0.486099811	None	None	N
E/L	0.6099	likely_pathogenic	0.5828	pathogenic	0.547	Stabilizing	0.986	D	0.723	prob.delet.	None	None	None	None	N
E/M	0.5395	ambiguous	0.52	ambiguous	0.989	Stabilizing	0.998	D	0.774	deleterious	None	None	None	None	N
E/N	0.5738	likely_pathogenic	0.5419	ambiguous	-1.205	Destabilizing	0.985	D	0.686	prob.neutral	None	None	None	None	N
E/P	0.7516	likely_pathogenic	0.728	pathogenic	0.165	Stabilizing	0.977	D	0.82	deleterious	None	None	None	None	N
E/Q	0.2735	likely_benign	0.2617	benign	-0.976	Destabilizing	0.997	D	0.639	neutral	N	0.467609803	None	None	N
E/R	0.6546	likely_pathogenic	0.6095	pathogenic	-0.331	Destabilizing	0.997	D	0.73	prob.delet.	None	None	None	None	N
E/S	0.3968	ambiguous	0.3813	ambiguous	-1.589	Destabilizing	0.958	D	0.489	neutral	None	None	None	None	N
E/T	0.3081	likely_benign	0.2851	benign	-1.208	Destabilizing	0.164	N	0.349	neutral	None	None	None	None	N
E/V	0.2716	likely_benign	0.2477	benign	0.165	Stabilizing	0.974	D	0.685	prob.neutral	N	0.474739827	None	None	N
E/W	0.9768	likely_pathogenic	0.9723	pathogenic	0.416	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Y	0.8574	likely_pathogenic	0.8412	pathogenic	0.442	Stabilizing	1.0	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.