TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14965	45118;45119;45120	chr2:178622690;178622689;178622688	chr2:179487417;179487416;179487415
N2AB	13324	40195;40196;40197	chr2:178622690;178622689;178622688	chr2:179487417;179487416;179487415
N2A	12397	37414;37415;37416	chr2:178622690;178622689;178622688	chr2:179487417;179487416;179487415
N2B	5900	17923;17924;17925	chr2:178622690;178622689;178622688	chr2:179487417;179487416;179487415
Novex-1	6025	18298;18299;18300	chr2:178622690;178622689;178622688	chr2:179487417;179487416;179487415
Novex-2	6092	18499;18500;18501	chr2:178622690;178622689;178622688	chr2:179487417;179487416;179487415
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-101
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.0786
• 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/V	None	None	None	N	0.274	0.089	0.0551355673512	gnomAD-4.0.0	1.60816E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88334E-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	0.7271	likely_pathogenic	0.5807	pathogenic	-2.928	Highly Destabilizing	0.035	N	0.622	neutral	None	None	None	None	N
L/C	0.8261	likely_pathogenic	0.748	pathogenic	-2.316	Highly Destabilizing	0.935	D	0.735	prob.delet.	None	None	None	None	N
L/D	0.9875	likely_pathogenic	0.9694	pathogenic	-3.253	Highly Destabilizing	0.555	D	0.812	deleterious	None	None	None	None	N
L/E	0.9508	likely_pathogenic	0.9043	pathogenic	-3.01	Highly Destabilizing	0.555	D	0.8	deleterious	None	None	None	None	N
L/F	0.5138	ambiguous	0.3548	ambiguous	-1.696	Destabilizing	0.317	N	0.705	prob.neutral	N	0.510426929	None	None	N
L/G	0.9318	likely_pathogenic	0.8706	pathogenic	-3.464	Highly Destabilizing	0.555	D	0.799	deleterious	None	None	None	None	N
L/H	0.9183	likely_pathogenic	0.8748	pathogenic	-2.767	Highly Destabilizing	0.915	D	0.786	deleterious	D	0.630535392	None	None	N
L/I	0.075	likely_benign	0.0513	benign	-1.353	Destabilizing	None	N	0.264	neutral	N	0.471421051	None	None	N
L/K	0.9356	likely_pathogenic	0.8696	pathogenic	-2.126	Highly Destabilizing	0.555	D	0.781	deleterious	None	None	None	None	N
L/M	0.2181	likely_benign	0.1763	benign	-1.532	Destabilizing	0.38	N	0.683	prob.neutral	None	None	None	None	N
L/N	0.9135	likely_pathogenic	0.8059	pathogenic	-2.548	Highly Destabilizing	0.791	D	0.818	deleterious	None	None	None	None	N
L/P	0.9079	likely_pathogenic	0.8344	pathogenic	-1.864	Destabilizing	0.741	D	0.813	deleterious	D	0.564288665	None	None	N
L/Q	0.8815	likely_pathogenic	0.8293	pathogenic	-2.387	Highly Destabilizing	0.791	D	0.787	deleterious	None	None	None	None	N
L/R	0.9127	likely_pathogenic	0.8394	pathogenic	-1.848	Destabilizing	0.484	N	0.793	deleterious	D	0.630535392	None	None	N
L/S	0.9067	likely_pathogenic	0.8086	pathogenic	-3.236	Highly Destabilizing	0.262	N	0.772	deleterious	None	None	None	None	N
L/T	0.6395	likely_pathogenic	0.4725	ambiguous	-2.851	Highly Destabilizing	0.149	N	0.685	prob.neutral	None	None	None	None	N
L/V	0.0931	likely_benign	0.0827	benign	-1.864	Destabilizing	None	N	0.274	neutral	N	0.38277302	None	None	N
L/W	0.8991	likely_pathogenic	0.8592	pathogenic	-2.01	Highly Destabilizing	0.935	D	0.755	deleterious	None	None	None	None	N
L/Y	0.8979	likely_pathogenic	0.8186	pathogenic	-1.831	Destabilizing	0.555	D	0.778	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.