TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5346	16261;16262;16263	chr2:178733257;178733256;178733255	chr2:179597984;179597983;179597982
N2AB	5029	15310;15311;15312	chr2:178733257;178733256;178733255	chr2:179597984;179597983;179597982
N2A	4102	12529;12530;12531	chr2:178733257;178733256;178733255	chr2:179597984;179597983;179597982
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-36
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.1014
• 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
T/I	rs1010676727	0.059	0.959	N	0.752	0.395	0.452737964553	gnomAD-2.1.1	4.17E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.26E-06	0
T/I	rs1010676727	0.059	0.959	N	0.752	0.395	0.452737964553	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
T/I	rs1010676727	0.059	0.959	N	0.752	0.395	0.452737964553	gnomAD-4.0.0	1.93318E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.55457E-05	0	1.61207E-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
T/A	0.1087	likely_benign	0.1023	benign	-1.144	Destabilizing	0.061	N	0.151	neutral	N	0.369147716	None	None	N
T/C	0.5787	likely_pathogenic	0.5765	pathogenic	-0.869	Destabilizing	0.046	N	0.323	neutral	None	None	None	None	N
T/D	0.7117	likely_pathogenic	0.6938	pathogenic	-1.311	Destabilizing	0.991	D	0.765	deleterious	None	None	None	None	N
T/E	0.6811	likely_pathogenic	0.6532	pathogenic	-1.135	Destabilizing	0.991	D	0.762	deleterious	None	None	None	None	N
T/F	0.6258	likely_pathogenic	0.5931	pathogenic	-0.755	Destabilizing	0.997	D	0.773	deleterious	None	None	None	None	N
T/G	0.4043	ambiguous	0.3965	ambiguous	-1.567	Destabilizing	0.939	D	0.697	prob.neutral	None	None	None	None	N
T/H	0.6365	likely_pathogenic	0.6043	pathogenic	-1.694	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
T/I	0.3705	ambiguous	0.3412	ambiguous	-0.043	Destabilizing	0.959	D	0.752	deleterious	N	0.473104377	None	None	N
T/K	0.6567	likely_pathogenic	0.5971	pathogenic	-0.723	Destabilizing	0.991	D	0.755	deleterious	None	None	None	None	N
T/L	0.2605	likely_benign	0.2408	benign	-0.043	Destabilizing	0.939	D	0.651	neutral	None	None	None	None	N
T/M	0.1421	likely_benign	0.1279	benign	0.028	Stabilizing	0.997	D	0.729	prob.delet.	None	None	None	None	N
T/N	0.2812	likely_benign	0.2489	benign	-1.311	Destabilizing	0.996	D	0.718	prob.delet.	D	0.524824063	None	None	N
T/P	0.8377	likely_pathogenic	0.8249	pathogenic	-0.377	Destabilizing	0.988	D	0.766	deleterious	N	0.519071527	None	None	N
T/Q	0.5926	likely_pathogenic	0.5539	ambiguous	-1.134	Destabilizing	0.997	D	0.77	deleterious	None	None	None	None	N
T/R	0.5986	likely_pathogenic	0.5402	ambiguous	-0.867	Destabilizing	0.991	D	0.761	deleterious	None	None	None	None	N
T/S	0.1995	likely_benign	0.1925	benign	-1.563	Destabilizing	0.704	D	0.606	neutral	N	0.452750534	None	None	N
T/V	0.2339	likely_benign	0.2203	benign	-0.377	Destabilizing	0.939	D	0.621	neutral	None	None	None	None	N
T/W	0.913	likely_pathogenic	0.9025	pathogenic	-0.844	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	N
T/Y	0.643	likely_pathogenic	0.6035	pathogenic	-0.509	Destabilizing	0.997	D	0.751	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.