TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6244	18955;18956;18957	chr2:178729426;178729425;178729424	chr2:179594153;179594152;179594151
N2AB	5927	18004;18005;18006	chr2:178729426;178729425;178729424	chr2:179594153;179594152;179594151
N2A	5000	15223;15224;15225	chr2:178729426;178729425;178729424	chr2:179594153;179594152;179594151
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-46
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.1894
• 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/E	None	None	0.996	N	0.418	0.29	0.277317399466	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/N	None	None	0.884	N	0.257	0.179	0.0297737177859	gnomAD-4.0.0	1.5916E-06	None	None	None	None	N	None	0	0	None	0	2.77316E-05	None	0	0	0	0	0
K/R	rs1448766260	-0.378	0.998	N	0.501	0.186	0.17258766438	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/R	rs1448766260	-0.378	0.998	N	0.501	0.186	0.17258766438	gnomAD-4.0.0	1.5916E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.0248E-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
K/A	0.7502	likely_pathogenic	0.7249	pathogenic	-0.691	Destabilizing	0.998	D	0.546	neutral	None	None	None	None	N
K/C	0.9243	likely_pathogenic	0.9149	pathogenic	-0.639	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
K/D	0.8134	likely_pathogenic	0.7896	pathogenic	0.069	Stabilizing	0.998	D	0.643	neutral	None	None	None	None	N
K/E	0.6127	likely_pathogenic	0.5939	pathogenic	0.165	Stabilizing	0.996	D	0.418	neutral	N	0.459846397	None	None	N
K/F	0.9382	likely_pathogenic	0.9321	pathogenic	-0.591	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/G	0.8159	likely_pathogenic	0.7853	pathogenic	-1.021	Destabilizing	0.997	D	0.579	neutral	None	None	None	None	N
K/H	0.5464	ambiguous	0.5228	ambiguous	-1.392	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
K/I	0.6568	likely_pathogenic	0.6489	pathogenic	0.147	Stabilizing	1.0	D	0.743	deleterious	N	0.477634711	None	None	N
K/L	0.6788	likely_pathogenic	0.6676	pathogenic	0.147	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	N
K/M	0.5254	ambiguous	0.504	ambiguous	0.125	Stabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
K/N	0.6365	likely_pathogenic	0.6185	pathogenic	-0.387	Destabilizing	0.884	D	0.257	neutral	N	0.504117064	None	None	N
K/P	0.9274	likely_pathogenic	0.8867	pathogenic	-0.102	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
K/Q	0.3677	ambiguous	0.3526	ambiguous	-0.476	Destabilizing	0.999	D	0.669	neutral	N	0.463974227	None	None	N
K/R	0.1138	likely_benign	0.1085	benign	-0.508	Destabilizing	0.998	D	0.501	neutral	N	0.441196162	None	None	N
K/S	0.7989	likely_pathogenic	0.7789	pathogenic	-1.101	Destabilizing	0.997	D	0.463	neutral	None	None	None	None	N
K/T	0.4488	ambiguous	0.453	ambiguous	-0.795	Destabilizing	0.999	D	0.681	prob.neutral	N	0.511101751	None	None	N
K/V	0.6631	likely_pathogenic	0.6456	pathogenic	-0.102	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/W	0.913	likely_pathogenic	0.9015	pathogenic	-0.449	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
K/Y	0.7939	likely_pathogenic	0.767	pathogenic	-0.144	Destabilizing	1.0	D	0.713	prob.delet.	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.