TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16665	50218;50219;50220	chr2:178612532;178612531;178612530	chr2:179477259;179477258;179477257
N2AB	15024	45295;45296;45297	chr2:178612532;178612531;178612530	chr2:179477259;179477258;179477257
N2A	14097	42514;42515;42516	chr2:178612532;178612531;178612530	chr2:179477259;179477258;179477257
N2B	7600	23023;23024;23025	chr2:178612532;178612531;178612530	chr2:179477259;179477258;179477257
Novex-1	7725	23398;23399;23400	chr2:178612532;178612531;178612530	chr2:179477259;179477258;179477257
Novex-2	7792	23599;23600;23601	chr2:178612532;178612531;178612530	chr2:179477259;179477258;179477257
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-9
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.3217
• 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
K/R	None	None	0.031	N	0.099	0.113	0.18274738541	gnomAD-4.0.0	1.59558E-06	None	None	None	None	N	None	5.67537E-05	0	None	0	0	None	0	0	0	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
K/A	0.7998	likely_pathogenic	0.8615	pathogenic	-0.229	Destabilizing	0.97	D	0.527	neutral	None	None	None	None	N
K/C	0.9596	likely_pathogenic	0.9694	pathogenic	-0.431	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/D	0.9571	likely_pathogenic	0.9733	pathogenic	-0.727	Destabilizing	0.996	D	0.528	neutral	None	None	None	None	N
K/E	0.7453	likely_pathogenic	0.8315	pathogenic	-0.707	Destabilizing	0.961	D	0.486	neutral	N	0.474450996	None	None	N
K/F	0.9932	likely_pathogenic	0.9959	pathogenic	-0.551	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
K/G	0.8318	likely_pathogenic	0.8877	pathogenic	-0.482	Destabilizing	0.985	D	0.58	neutral	None	None	None	None	N
K/H	0.7996	likely_pathogenic	0.8488	pathogenic	-1.027	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	N
K/I	0.9391	likely_pathogenic	0.961	pathogenic	0.375	Stabilizing	0.998	D	0.702	prob.neutral	D	0.559992165	None	None	N
K/L	0.903	likely_pathogenic	0.9338	pathogenic	0.375	Stabilizing	0.97	D	0.58	neutral	None	None	None	None	N
K/M	0.8702	likely_pathogenic	0.9085	pathogenic	0.553	Stabilizing	1.0	D	0.56	neutral	None	None	None	None	N
K/N	0.9203	likely_pathogenic	0.9436	pathogenic	-0.277	Destabilizing	0.98	D	0.489	neutral	N	0.479683346	None	None	N
K/P	0.8581	likely_pathogenic	0.9038	pathogenic	0.202	Stabilizing	0.999	D	0.565	neutral	None	None	None	None	N
K/Q	0.4617	ambiguous	0.5306	ambiguous	-0.606	Destabilizing	0.961	D	0.537	neutral	N	0.477730807	None	None	N
K/R	0.1045	likely_benign	0.1028	benign	-0.251	Destabilizing	0.031	N	0.099	neutral	N	0.447996192	None	None	N
K/S	0.8675	likely_pathogenic	0.9079	pathogenic	-0.738	Destabilizing	0.985	D	0.45	neutral	None	None	None	None	N
K/T	0.7642	likely_pathogenic	0.8448	pathogenic	-0.562	Destabilizing	0.98	D	0.522	neutral	N	0.4709756	None	None	N
K/V	0.8831	likely_pathogenic	0.9183	pathogenic	0.202	Stabilizing	0.996	D	0.564	neutral	None	None	None	None	N
K/W	0.9817	likely_pathogenic	0.9891	pathogenic	-0.509	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
K/Y	0.9732	likely_pathogenic	0.9823	pathogenic	-0.088	Destabilizing	0.999	D	0.675	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.