TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7160	21703;21704;21705	chr2:178723622;178723621;178723620	chr2:179588349;179588348;179588347
N2AB	6843	20752;20753;20754	chr2:178723622;178723621;178723620	chr2:179588349;179588348;179588347
N2A	5916	17971;17972;17973	chr2:178723622;178723621;178723620	chr2:179588349;179588348;179588347
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-56
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1034
• 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
I/T	None	None	0.642	D	0.675	0.435	0.734902578319	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-06	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
I/A	0.8131	likely_pathogenic	0.8222	pathogenic	-2.013	Highly Destabilizing	0.329	N	0.586	neutral	None	None	None	None	N
I/C	0.9118	likely_pathogenic	0.9151	pathogenic	-1.247	Destabilizing	0.995	D	0.755	deleterious	None	None	None	None	N
I/D	0.9947	likely_pathogenic	0.9945	pathogenic	-1.806	Destabilizing	0.981	D	0.821	deleterious	None	None	None	None	N
I/E	0.9824	likely_pathogenic	0.982	pathogenic	-1.507	Destabilizing	0.944	D	0.809	deleterious	None	None	None	None	N
I/F	0.2922	likely_benign	0.2797	benign	-1.042	Destabilizing	0.006	N	0.376	neutral	D	0.530792817	None	None	N
I/G	0.9647	likely_pathogenic	0.9676	pathogenic	-2.619	Highly Destabilizing	0.828	D	0.789	deleterious	None	None	None	None	N
I/H	0.9667	likely_pathogenic	0.9654	pathogenic	-2.227	Highly Destabilizing	0.995	D	0.803	deleterious	None	None	None	None	N
I/K	0.9596	likely_pathogenic	0.9588	pathogenic	-1.226	Destabilizing	0.944	D	0.801	deleterious	None	None	None	None	N
I/L	0.1481	likely_benign	0.1626	benign	-0.24	Destabilizing	0.002	N	0.218	neutral	N	0.490868992	None	None	N
I/M	0.1875	likely_benign	0.1989	benign	-0.364	Destabilizing	0.139	N	0.391	neutral	N	0.512376002	None	None	N
I/N	0.9372	likely_pathogenic	0.9363	pathogenic	-1.725	Destabilizing	0.975	D	0.823	deleterious	D	0.530987236	None	None	N
I/P	0.9751	likely_pathogenic	0.9747	pathogenic	-0.814	Destabilizing	0.981	D	0.821	deleterious	None	None	None	None	N
I/Q	0.956	likely_pathogenic	0.9554	pathogenic	-1.381	Destabilizing	0.944	D	0.82	deleterious	None	None	None	None	N
I/R	0.9387	likely_pathogenic	0.9372	pathogenic	-1.394	Destabilizing	0.944	D	0.822	deleterious	None	None	None	None	N
I/S	0.8837	likely_pathogenic	0.8869	pathogenic	-2.487	Highly Destabilizing	0.784	D	0.747	deleterious	N	0.512284414	None	None	N
I/T	0.8005	likely_pathogenic	0.7999	pathogenic	-2.012	Highly Destabilizing	0.642	D	0.675	prob.neutral	D	0.527136436	None	None	N
I/V	0.1129	likely_benign	0.1158	benign	-0.814	Destabilizing	0.001	N	0.183	neutral	N	0.407124527	None	None	N
I/W	0.9535	likely_pathogenic	0.9529	pathogenic	-1.379	Destabilizing	0.995	D	0.799	deleterious	None	None	None	None	N
I/Y	0.8732	likely_pathogenic	0.8705	pathogenic	-1.052	Destabilizing	0.807	D	0.769	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.