TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14002	42229;42230;42231	chr2:178635185;178635184;178635183	chr2:179499912;179499911;179499910
N2AB	12361	37306;37307;37308	chr2:178635185;178635184;178635183	chr2:179499912;179499911;179499910
N2A	11434	34525;34526;34527	chr2:178635185;178635184;178635183	chr2:179499912;179499911;179499910
N2B	4937	15034;15035;15036	chr2:178635185;178635184;178635183	chr2:179499912;179499911;179499910
Novex-1	5062	15409;15410;15411	chr2:178635185;178635184;178635183	chr2:179499912;179499911;179499910
Novex-2	5129	15610;15611;15612	chr2:178635185;178635184;178635183	chr2:179499912;179499911;179499910
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-90
• Domain position: 38
• Structural Position: 55
• Q(SASA): 0.4929
• 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/K	None	None	0.91	N	0.463	0.231	0.180583059064	gnomAD-4.0.0	2.05374E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7995E-06	0	1.65788E-05

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	0.7887	likely_pathogenic	0.6167	pathogenic	-0.344	Destabilizing	0.953	D	0.443	neutral	N	0.423454814	None	None	N
E/C	0.9919	likely_pathogenic	0.9836	pathogenic	-0.329	Destabilizing	1.0	D	0.622	neutral	None	None	None	None	N
E/D	0.4423	ambiguous	0.2576	benign	-0.398	Destabilizing	0.953	D	0.449	neutral	N	0.43485487	None	None	N
E/F	0.9885	likely_pathogenic	0.9733	pathogenic	-0.007	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	N
E/G	0.8761	likely_pathogenic	0.7456	pathogenic	-0.56	Destabilizing	0.993	D	0.423	neutral	N	0.458155103	None	None	N
E/H	0.9536	likely_pathogenic	0.8927	pathogenic	0.419	Stabilizing	0.999	D	0.495	neutral	None	None	None	None	N
E/I	0.9035	likely_pathogenic	0.7926	pathogenic	0.197	Stabilizing	0.998	D	0.66	prob.neutral	None	None	None	None	N
E/K	0.8321	likely_pathogenic	0.6511	pathogenic	0.244	Stabilizing	0.91	D	0.463	neutral	N	0.433987894	None	None	N
E/L	0.9513	likely_pathogenic	0.8807	pathogenic	0.197	Stabilizing	0.99	D	0.585	neutral	None	None	None	None	N
E/M	0.9415	likely_pathogenic	0.8725	pathogenic	0.085	Stabilizing	1.0	D	0.501	neutral	None	None	None	None	N
E/N	0.7983	likely_pathogenic	0.6178	pathogenic	-0.288	Destabilizing	0.995	D	0.523	neutral	None	None	None	None	N
E/P	0.9977	likely_pathogenic	0.9919	pathogenic	0.036	Stabilizing	0.998	D	0.524	neutral	None	None	None	None	N
E/Q	0.5671	likely_pathogenic	0.3953	ambiguous	-0.207	Destabilizing	0.441	N	0.257	neutral	N	0.430620474	None	None	N
E/R	0.9021	likely_pathogenic	0.8027	pathogenic	0.598	Stabilizing	0.99	D	0.51	neutral	None	None	None	None	N
E/S	0.7984	likely_pathogenic	0.6343	pathogenic	-0.422	Destabilizing	0.964	D	0.489	neutral	None	None	None	None	N
E/T	0.8152	likely_pathogenic	0.6482	pathogenic	-0.232	Destabilizing	0.995	D	0.515	neutral	None	None	None	None	N
E/V	0.8019	likely_pathogenic	0.6282	pathogenic	0.036	Stabilizing	0.993	D	0.511	neutral	N	0.430202296	None	None	N
E/W	0.9981	likely_pathogenic	0.9953	pathogenic	0.193	Stabilizing	1.0	D	0.624	neutral	None	None	None	None	N
E/Y	0.9784	likely_pathogenic	0.9508	pathogenic	0.246	Stabilizing	0.998	D	0.535	neutral	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.