TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8468	25627;25628;25629	chr2:178717332;178717331;178717330	chr2:179582059;179582058;179582057
N2AB	8151	24676;24677;24678	chr2:178717332;178717331;178717330	chr2:179582059;179582058;179582057
N2A	7224	21895;21896;21897	chr2:178717332;178717331;178717330	chr2:179582059;179582058;179582057
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-70
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.4753
• 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
A/V	rs762161074	-0.113	0.026	N	0.223	0.162	0.321672782286	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
A/V	rs762161074	-0.113	0.026	N	0.223	0.162	0.321672782286	gnomAD-4.0.0	1.59207E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86028E-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
A/C	0.6323	likely_pathogenic	0.5893	pathogenic	-0.793	Destabilizing	0.994	D	0.35	neutral	None	None	None	None	N
A/D	0.2917	likely_benign	0.2629	benign	-0.551	Destabilizing	0.91	D	0.482	neutral	N	0.470240217	None	None	N
A/E	0.2373	likely_benign	0.218	benign	-0.657	Destabilizing	0.725	D	0.36	neutral	None	None	None	None	N
A/F	0.268	likely_benign	0.2612	benign	-0.782	Destabilizing	0.961	D	0.501	neutral	None	None	None	None	N
A/G	0.1406	likely_benign	0.1398	benign	-0.621	Destabilizing	0.122	N	0.295	neutral	N	0.504083431	None	None	N
A/H	0.4036	ambiguous	0.3654	ambiguous	-0.629	Destabilizing	0.998	D	0.482	neutral	None	None	None	None	N
A/I	0.1712	likely_benign	0.1645	benign	-0.271	Destabilizing	0.779	D	0.354	neutral	None	None	None	None	N
A/K	0.3592	ambiguous	0.2903	benign	-0.9	Destabilizing	0.876	D	0.365	neutral	None	None	None	None	N
A/L	0.1246	likely_benign	0.1228	benign	-0.271	Destabilizing	0.022	N	0.239	neutral	None	None	None	None	N
A/M	0.2034	likely_benign	0.2043	benign	-0.353	Destabilizing	0.961	D	0.38	neutral	None	None	None	None	N
A/N	0.2317	likely_benign	0.211	benign	-0.569	Destabilizing	0.611	D	0.491	neutral	None	None	None	None	N
A/P	0.0886	likely_benign	0.086	benign	-0.3	Destabilizing	0.004	N	0.275	neutral	N	0.4405921	None	None	N
A/Q	0.2675	likely_benign	0.2462	benign	-0.799	Destabilizing	0.98	D	0.395	neutral	None	None	None	None	N
A/R	0.3252	likely_benign	0.2806	benign	-0.449	Destabilizing	0.98	D	0.396	neutral	None	None	None	None	N
A/S	0.0913	likely_benign	0.0917	benign	-0.85	Destabilizing	0.05	N	0.304	neutral	N	0.43747165	None	None	N
A/T	0.0877	likely_benign	0.0862	benign	-0.868	Destabilizing	0.005	N	0.171	neutral	N	0.423929137	None	None	N
A/V	0.0976	likely_benign	0.0963	benign	-0.3	Destabilizing	0.026	N	0.223	neutral	N	0.41267478	None	None	N
A/W	0.7064	likely_pathogenic	0.6837	pathogenic	-0.992	Destabilizing	0.998	D	0.55	neutral	None	None	None	None	N
A/Y	0.4391	ambiguous	0.418	ambiguous	-0.63	Destabilizing	0.993	D	0.492	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.