TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29500	88723;88724;88725	chr2:178554961;178554960;178554959	chr2:179419688;179419687;179419686
N2AB	27859	83800;83801;83802	chr2:178554961;178554960;178554959	chr2:179419688;179419687;179419686
N2A	26932	81019;81020;81021	chr2:178554961;178554960;178554959	chr2:179419688;179419687;179419686
N2B	20435	61528;61529;61530	chr2:178554961;178554960;178554959	chr2:179419688;179419687;179419686
Novex-1	20560	61903;61904;61905	chr2:178554961;178554960;178554959	chr2:179419688;179419687;179419686
Novex-2	20627	62104;62105;62106	chr2:178554961;178554960;178554959	chr2:179419688;179419687;179419686
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-146
• Domain position: 57
• Structural Position: 140
• Q(SASA): 0.1223
• 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
I/L	rs761934380	-0.954	0.005	D	0.299	0.374	0.585808247695	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.30745E-04	None	0	0	0
I/L	rs761934380	-0.954	0.005	D	0.299	0.374	0.585808247695	gnomAD-4.0.0	7.52669E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9946E-07	9.27472E-05	3.31334E-05
I/M	None	None	0.976	D	0.697	0.749	0.716492818265	gnomAD-4.0.0	6.84265E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99493E-07	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
I/A	0.9549	likely_pathogenic	0.9653	pathogenic	-2.755	Highly Destabilizing	0.863	D	0.689	prob.neutral	None	None	None	None	N
I/C	0.9247	likely_pathogenic	0.9379	pathogenic	-2.105	Highly Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
I/D	0.9948	likely_pathogenic	0.9958	pathogenic	-2.932	Highly Destabilizing	0.997	D	0.852	deleterious	None	None	None	None	N
I/E	0.9829	likely_pathogenic	0.9852	pathogenic	-2.715	Highly Destabilizing	0.997	D	0.847	deleterious	None	None	None	None	N
I/F	0.3769	ambiguous	0.4168	ambiguous	-1.625	Destabilizing	0.976	D	0.733	prob.delet.	D	0.55136203	None	None	N
I/G	0.9881	likely_pathogenic	0.9911	pathogenic	-3.308	Highly Destabilizing	0.997	D	0.83	deleterious	None	None	None	None	N
I/H	0.9572	likely_pathogenic	0.9636	pathogenic	-2.647	Highly Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
I/K	0.9572	likely_pathogenic	0.9627	pathogenic	-2.304	Highly Destabilizing	0.997	D	0.833	deleterious	None	None	None	None	N
I/L	0.1752	likely_benign	0.1926	benign	-1.16	Destabilizing	0.005	N	0.299	neutral	D	0.530537943	None	None	N
I/M	0.2036	likely_benign	0.2265	benign	-1.095	Destabilizing	0.976	D	0.697	prob.neutral	D	0.573710557	None	None	N
I/N	0.9393	likely_pathogenic	0.9508	pathogenic	-2.603	Highly Destabilizing	0.996	D	0.851	deleterious	D	0.600661299	None	None	N
I/P	0.9913	likely_pathogenic	0.9923	pathogenic	-1.672	Destabilizing	0.997	D	0.853	deleterious	None	None	None	None	N
I/Q	0.9444	likely_pathogenic	0.9524	pathogenic	-2.48	Highly Destabilizing	0.997	D	0.848	deleterious	None	None	None	None	N
I/R	0.9343	likely_pathogenic	0.9444	pathogenic	-1.915	Destabilizing	0.997	D	0.852	deleterious	None	None	None	None	N
I/S	0.9478	likely_pathogenic	0.9577	pathogenic	-3.337	Highly Destabilizing	0.988	D	0.811	deleterious	D	0.584641938	None	None	N
I/T	0.9472	likely_pathogenic	0.9569	pathogenic	-2.971	Highly Destabilizing	0.92	D	0.695	prob.neutral	D	0.60025769	None	None	N
I/V	0.169	likely_benign	0.1825	benign	-1.672	Destabilizing	0.061	N	0.291	neutral	D	0.556341695	None	None	N
I/W	0.9274	likely_pathogenic	0.9386	pathogenic	-1.978	Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
I/Y	0.8815	likely_pathogenic	0.8977	pathogenic	-1.736	Destabilizing	0.997	D	0.791	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.