TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1706	5341;5342;5343	chr2:178776748;178776747;178776746	chr2:179641475;179641474;179641473
N2AB	1706	5341;5342;5343	chr2:178776748;178776747;178776746	chr2:179641475;179641474;179641473
N2A	1706	5341;5342;5343	chr2:178776748;178776747;178776746	chr2:179641475;179641474;179641473
N2B	1660	5203;5204;5205	chr2:178776748;178776747;178776746	chr2:179641475;179641474;179641473
Novex-1	1660	5203;5204;5205	chr2:178776748;178776747;178776746	chr2:179641475;179641474;179641473
Novex-2	1660	5203;5204;5205	chr2:178776748;178776747;178776746	chr2:179641475;179641474;179641473
Novex-3	1706	5341;5342;5343	chr2:178776748;178776747;178776746	chr2:179641475;179641474;179641473

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-8
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.8703
• Predicted PPI site: I

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	0.575	0.464	0.48095081912	gnomAD-4.0.0	1.08029E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.18125E-05	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	0.9704	likely_pathogenic	0.9618	pathogenic	-0.176	Destabilizing	0.998	D	0.624	neutral	None	None	None	None	I
K/C	0.9808	likely_pathogenic	0.9758	pathogenic	-0.481	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
K/D	0.9953	likely_pathogenic	0.9944	pathogenic	0.083	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
K/E	0.9604	likely_pathogenic	0.9433	pathogenic	0.14	Stabilizing	0.996	D	0.575	neutral	N	0.512679285	None	None	I
K/F	0.9944	likely_pathogenic	0.9936	pathogenic	-0.216	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
K/G	0.9735	likely_pathogenic	0.9647	pathogenic	-0.421	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	I
K/H	0.8689	likely_pathogenic	0.8423	pathogenic	-0.546	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
K/I	0.9495	likely_pathogenic	0.9455	pathogenic	0.408	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
K/L	0.9121	likely_pathogenic	0.8996	pathogenic	0.408	Stabilizing	1.0	D	0.648	neutral	None	None	None	None	I
K/M	0.9275	likely_pathogenic	0.9119	pathogenic	-0.025	Destabilizing	1.0	D	0.75	deleterious	N	0.516965026	None	None	I
K/N	0.9876	likely_pathogenic	0.9857	pathogenic	-0.113	Destabilizing	0.999	D	0.747	deleterious	N	0.519315538	None	None	I
K/P	0.9829	likely_pathogenic	0.9798	pathogenic	0.242	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
K/Q	0.6962	likely_pathogenic	0.6265	pathogenic	-0.167	Destabilizing	0.999	D	0.727	prob.delet.	N	0.510990097	None	None	I
K/R	0.1467	likely_benign	0.1301	benign	-0.131	Destabilizing	0.884	D	0.289	neutral	N	0.513411983	None	None	I
K/S	0.9809	likely_pathogenic	0.9758	pathogenic	-0.615	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	I
K/T	0.9085	likely_pathogenic	0.8948	pathogenic	-0.385	Destabilizing	0.999	D	0.723	prob.delet.	N	0.365259817	None	None	I
K/V	0.9277	likely_pathogenic	0.9201	pathogenic	0.242	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
K/W	0.9877	likely_pathogenic	0.9832	pathogenic	-0.232	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
K/Y	0.9801	likely_pathogenic	0.9767	pathogenic	0.101	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	I

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.