TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1723	5392;5393;5394	chr2:178776697;178776696;178776695	chr2:179641424;179641423;179641422
N2AB	1723	5392;5393;5394	chr2:178776697;178776696;178776695	chr2:179641424;179641423;179641422
N2A	1723	5392;5393;5394	chr2:178776697;178776696;178776695	chr2:179641424;179641423;179641422
N2B	1677	5254;5255;5256	chr2:178776697;178776696;178776695	chr2:179641424;179641423;179641422
Novex-1	1677	5254;5255;5256	chr2:178776697;178776696;178776695	chr2:179641424;179641423;179641422
Novex-2	1677	5254;5255;5256	chr2:178776697;178776696;178776695	chr2:179641424;179641423;179641422
Novex-3	1723	5392;5393;5394	chr2:178776697;178776696;178776695	chr2:179641424;179641423;179641422

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-8
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.2458
• 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
E/Q	rs2092262638	None	1.0	D	0.623	0.473	0.470484629704	gnomAD-4.0.0	1.59067E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85654E-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	0.6568	likely_pathogenic	0.5978	pathogenic	-0.88	Destabilizing	0.999	D	0.589	neutral	D	0.652798413	None	None	I
E/C	0.9909	likely_pathogenic	0.9864	pathogenic	-0.66	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
E/D	0.3076	likely_benign	0.2773	benign	-1.497	Destabilizing	0.999	D	0.481	neutral	N	0.51113246	None	None	I
E/F	0.9865	likely_pathogenic	0.9797	pathogenic	-0.157	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
E/G	0.8147	likely_pathogenic	0.7917	pathogenic	-1.322	Destabilizing	1.0	D	0.671	neutral	D	0.682067013	None	None	I
E/H	0.9293	likely_pathogenic	0.886	pathogenic	-0.612	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
E/I	0.9042	likely_pathogenic	0.8811	pathogenic	0.358	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
E/K	0.8629	likely_pathogenic	0.8304	pathogenic	-1.336	Destabilizing	0.999	D	0.539	neutral	D	0.584151158	None	None	I
E/L	0.9427	likely_pathogenic	0.9179	pathogenic	0.358	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
E/M	0.9519	likely_pathogenic	0.9342	pathogenic	0.964	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
E/N	0.7902	likely_pathogenic	0.7353	pathogenic	-1.763	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
E/P	0.9917	likely_pathogenic	0.9899	pathogenic	-0.034	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
E/Q	0.5581	ambiguous	0.4792	ambiguous	-1.504	Destabilizing	1.0	D	0.623	neutral	D	0.581068828	None	None	I
E/R	0.8859	likely_pathogenic	0.8423	pathogenic	-1.067	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
E/S	0.6235	likely_pathogenic	0.5428	ambiguous	-2.216	Highly Destabilizing	0.999	D	0.603	neutral	None	None	None	None	I
E/T	0.7475	likely_pathogenic	0.6929	pathogenic	-1.843	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
E/V	0.7705	likely_pathogenic	0.7261	pathogenic	-0.034	Destabilizing	1.0	D	0.708	prob.delet.	D	0.576615341	None	None	I
E/W	0.9964	likely_pathogenic	0.9938	pathogenic	-0.044	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
E/Y	0.9745	likely_pathogenic	0.9605	pathogenic	0.028	Stabilizing	1.0	D	0.767	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.