TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15077	45454;45455;45456	chr2:178621595;178621594;178621593	chr2:179486322;179486321;179486320
N2AB	13436	40531;40532;40533	chr2:178621595;178621594;178621593	chr2:179486322;179486321;179486320
N2A	12509	37750;37751;37752	chr2:178621595;178621594;178621593	chr2:179486322;179486321;179486320
N2B	6012	18259;18260;18261	chr2:178621595;178621594;178621593	chr2:179486322;179486321;179486320
Novex-1	6137	18634;18635;18636	chr2:178621595;178621594;178621593	chr2:179486322;179486321;179486320
Novex-2	6204	18835;18836;18837	chr2:178621595;178621594;178621593	chr2:179486322;179486321;179486320
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: Ig-102
• Domain position: 47
• Structural Position: 122
• Q(SASA): 0.3996
• 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/G	None	None	0.999	D	0.677	0.424	0.55046033382	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.2482	likely_benign	0.2767	benign	-0.908	Destabilizing	0.998	D	0.609	neutral	D	0.553065249	None	None	N
E/C	0.8992	likely_pathogenic	0.9395	pathogenic	-0.458	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/D	0.1697	likely_benign	0.2038	benign	-1.163	Destabilizing	0.434	N	0.217	neutral	N	0.504557869	None	None	N
E/F	0.8528	likely_pathogenic	0.887	pathogenic	-0.393	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/G	0.2676	likely_benign	0.2893	benign	-1.28	Destabilizing	0.999	D	0.677	prob.neutral	D	0.566355013	None	None	N
E/H	0.4639	ambiguous	0.5553	ambiguous	-0.685	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/I	0.5104	ambiguous	0.5466	ambiguous	0.11	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/K	0.1628	likely_benign	0.1868	benign	-0.527	Destabilizing	0.998	D	0.518	neutral	N	0.506833239	None	None	N
E/L	0.5978	likely_pathogenic	0.6498	pathogenic	0.11	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/M	0.6028	likely_pathogenic	0.6459	pathogenic	0.566	Stabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
E/N	0.2994	likely_benign	0.3628	ambiguous	-1.028	Destabilizing	0.999	D	0.666	neutral	None	None	None	None	N
E/P	0.9685	likely_pathogenic	0.9744	pathogenic	-0.208	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/Q	0.1409	likely_benign	0.1622	benign	-0.896	Destabilizing	0.999	D	0.621	neutral	N	0.508878067	None	None	N
E/R	0.2665	likely_benign	0.3202	benign	-0.316	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
E/S	0.2455	likely_benign	0.2914	benign	-1.359	Destabilizing	0.997	D	0.549	neutral	None	None	None	None	N
E/T	0.2637	likely_benign	0.3035	benign	-1.041	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
E/V	0.3344	likely_benign	0.3626	ambiguous	-0.208	Destabilizing	1.0	D	0.775	deleterious	N	0.512130362	None	None	N
E/W	0.9405	likely_pathogenic	0.9588	pathogenic	-0.139	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/Y	0.7369	likely_pathogenic	0.7983	pathogenic	-0.12	Destabilizing	1.0	D	0.767	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.