TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25697	77314;77315;77316	chr2:178569043;178569042;178569041	chr2:179433770;179433769;179433768
N2AB	24056	72391;72392;72393	chr2:178569043;178569042;178569041	chr2:179433770;179433769;179433768
N2A	23129	69610;69611;69612	chr2:178569043;178569042;178569041	chr2:179433770;179433769;179433768
N2B	16632	50119;50120;50121	chr2:178569043;178569042;178569041	chr2:179433770;179433769;179433768
Novex-1	16757	50494;50495;50496	chr2:178569043;178569042;178569041	chr2:179433770;179433769;179433768
Novex-2	16824	50695;50696;50697	chr2:178569043;178569042;178569041	chr2:179433770;179433769;179433768
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: Fn3-74
• Domain position: 97
• Structural Position: 132
• Q(SASA): 1.3209
• 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/K	rs754291492	0.391	0.996	N	0.817	0.398	0.476127810785	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/K	rs754291492	0.391	0.996	N	0.817	0.398	0.476127810785	gnomAD-4.0.0	3.42208E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49823E-06	0	0
E/V	rs764509751	0.288	0.997	N	0.751	0.588	0.612105117874	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
E/V	rs764509751	0.288	0.997	N	0.751	0.588	0.612105117874	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/V	rs764509751	0.288	0.997	N	0.751	0.588	0.612105117874	gnomAD-4.0.0	1.85966E-06	None	None	None	None	N	None	0	0	None	3.38089E-05	0	None	0	0	1.69559E-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	0.3115	likely_benign	0.3198	benign	-0.268	Destabilizing	0.993	D	0.793	deleterious	N	0.512510048	None	None	N
E/C	0.9516	likely_pathogenic	0.9545	pathogenic	-0.144	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/D	0.3839	ambiguous	0.3825	ambiguous	-0.368	Destabilizing	0.946	D	0.681	prob.neutral	N	0.462910734	None	None	N
E/F	0.9633	likely_pathogenic	0.9669	pathogenic	-0.151	Destabilizing	1.0	D	0.737	deleterious	None	None	None	None	N
E/G	0.4291	ambiguous	0.4441	ambiguous	-0.446	Destabilizing	0.999	D	0.719	prob.delet.	N	0.507875019	None	None	N
E/H	0.8784	likely_pathogenic	0.8795	pathogenic	0.225	Stabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
E/I	0.8233	likely_pathogenic	0.8395	pathogenic	0.161	Stabilizing	0.998	D	0.739	deleterious	None	None	None	None	N
E/K	0.5909	likely_pathogenic	0.603	pathogenic	0.358	Stabilizing	0.996	D	0.817	deleterious	N	0.48608877	None	None	N
E/L	0.7963	likely_pathogenic	0.8182	pathogenic	0.161	Stabilizing	0.998	D	0.737	deleterious	None	None	None	None	N
E/M	0.7094	likely_pathogenic	0.7374	pathogenic	0.098	Stabilizing	0.997	D	0.791	deleterious	None	None	None	None	N
E/N	0.607	likely_pathogenic	0.638	pathogenic	-0.004	Destabilizing	0.996	D	0.826	deleterious	None	None	None	None	N
E/P	0.9876	likely_pathogenic	0.9872	pathogenic	0.038	Stabilizing	0.988	D	0.741	deleterious	None	None	None	None	N
E/Q	0.2514	likely_benign	0.2729	benign	0.029	Stabilizing	0.998	D	0.705	prob.delet.	N	0.508992527	None	None	N
E/R	0.7407	likely_pathogenic	0.7484	pathogenic	0.602	Stabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
E/S	0.411	ambiguous	0.4206	ambiguous	-0.137	Destabilizing	0.994	D	0.797	deleterious	None	None	None	None	N
E/T	0.5393	ambiguous	0.5405	ambiguous	0.012	Stabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
E/V	0.5633	ambiguous	0.5791	pathogenic	0.038	Stabilizing	0.997	D	0.751	deleterious	N	0.485835281	None	None	N
E/W	0.993	likely_pathogenic	0.9924	pathogenic	-0.019	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/Y	0.951	likely_pathogenic	0.9504	pathogenic	0.088	Stabilizing	1.0	D	0.758	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.