TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2285	7078;7079;7080	chr2:178774411;178774410;178774409	chr2:179639138;179639137;179639136
N2AB	2285	7078;7079;7080	chr2:178774411;178774410;178774409	chr2:179639138;179639137;179639136
N2A	2285	7078;7079;7080	chr2:178774411;178774410;178774409	chr2:179639138;179639137;179639136
N2B	2239	6940;6941;6942	chr2:178774411;178774410;178774409	chr2:179639138;179639137;179639136
Novex-1	2239	6940;6941;6942	chr2:178774411;178774410;178774409	chr2:179639138;179639137;179639136
Novex-2	2239	6940;6941;6942	chr2:178774411;178774410;178774409	chr2:179639138;179639137;179639136
Novex-3	2285	7078;7079;7080	chr2:178774411;178774410;178774409	chr2:179639138;179639137;179639136

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-12
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.2905
• 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/D	rs2091955390	None	0.999	N	0.522	0.203	0.0986583533028	gnomAD-4.0.0	6.84193E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99368E-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
E/A	0.2864	likely_benign	0.2609	benign	-0.555	Destabilizing	0.999	D	0.674	neutral	N	0.451171286	None	None	N
E/C	0.9251	likely_pathogenic	0.9202	pathogenic	-0.154	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
E/D	0.1836	likely_benign	0.1713	benign	-0.592	Destabilizing	0.999	D	0.522	neutral	N	0.453177417	None	None	N
E/F	0.8065	likely_pathogenic	0.7916	pathogenic	-0.243	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/G	0.4236	ambiguous	0.38	ambiguous	-0.816	Destabilizing	1.0	D	0.74	deleterious	N	0.445980807	None	None	N
E/H	0.6294	likely_pathogenic	0.5916	pathogenic	-0.211	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/I	0.3394	likely_benign	0.3307	benign	0.12	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/K	0.2954	likely_benign	0.261	benign	0.121	Stabilizing	0.999	D	0.603	neutral	N	0.416242724	None	None	N
E/L	0.5339	ambiguous	0.5146	ambiguous	0.12	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/M	0.5174	ambiguous	0.5027	ambiguous	0.322	Stabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
E/N	0.3421	ambiguous	0.321	benign	-0.333	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/P	0.9649	likely_pathogenic	0.9465	pathogenic	-0.084	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/Q	0.2029	likely_benign	0.1863	benign	-0.255	Destabilizing	1.0	D	0.668	neutral	N	0.448581409	None	None	N
E/R	0.5029	ambiguous	0.4566	ambiguous	0.34	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/S	0.296	likely_benign	0.278	benign	-0.505	Destabilizing	0.999	D	0.65	neutral	None	None	None	None	N
E/T	0.2636	likely_benign	0.2548	benign	-0.285	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/V	0.2249	likely_benign	0.2169	benign	-0.084	Destabilizing	1.0	D	0.76	deleterious	N	0.381677999	None	None	N
E/W	0.9632	likely_pathogenic	0.9567	pathogenic	-0.019	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/Y	0.7762	likely_pathogenic	0.7507	pathogenic	0.018	Stabilizing	1.0	D	0.775	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.