TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4865	14818;14819;14820	chr2:178735853;178735852;178735851	chr2:179600580;179600579;179600578
N2AB	4548	13867;13868;13869	chr2:178735853;178735852;178735851	chr2:179600580;179600579;179600578
N2A	3621	11086;11087;11088	chr2:178735853;178735852;178735851	chr2:179600580;179600579;179600578
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-31
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.0881
• 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
Y/C	None	None	1.0	D	0.869	0.891	0.891075467594	gnomAD-4.0.0	2.05263E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69835E-06	0	0
Y/N	None	None	1.0	D	0.882	0.895	0.923081794222	gnomAD-4.0.0	2.05265E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69838E-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
Y/A	0.9759	likely_pathogenic	0.9747	pathogenic	-2.17	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/C	0.732	likely_pathogenic	0.7407	pathogenic	-1.391	Destabilizing	1.0	D	0.869	deleterious	D	0.820911818	None	None	N
Y/D	0.9925	likely_pathogenic	0.9936	pathogenic	-2.867	Highly Destabilizing	1.0	D	0.882	deleterious	D	0.820911818	None	None	N
Y/E	0.9964	likely_pathogenic	0.9964	pathogenic	-2.614	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/F	0.1473	likely_benign	0.1224	benign	-0.678	Destabilizing	0.999	D	0.678	prob.neutral	D	0.644997618	None	None	N
Y/G	0.9759	likely_pathogenic	0.9738	pathogenic	-2.63	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/H	0.9137	likely_pathogenic	0.9039	pathogenic	-2.011	Highly Destabilizing	1.0	D	0.78	deleterious	D	0.821550483	None	None	N
Y/I	0.7119	likely_pathogenic	0.715	pathogenic	-0.65	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
Y/K	0.9952	likely_pathogenic	0.9951	pathogenic	-1.718	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/L	0.6981	likely_pathogenic	0.6961	pathogenic	-0.65	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
Y/M	0.9355	likely_pathogenic	0.929	pathogenic	-0.692	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
Y/N	0.9547	likely_pathogenic	0.9546	pathogenic	-2.661	Highly Destabilizing	1.0	D	0.882	deleterious	D	0.820911818	None	None	N
Y/P	0.9922	likely_pathogenic	0.9929	pathogenic	-1.173	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
Y/Q	0.9931	likely_pathogenic	0.9923	pathogenic	-2.199	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/R	0.9804	likely_pathogenic	0.9786	pathogenic	-2.032	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/S	0.9487	likely_pathogenic	0.9474	pathogenic	-2.954	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.820911818	None	None	N
Y/T	0.9738	likely_pathogenic	0.9731	pathogenic	-2.55	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/V	0.6629	likely_pathogenic	0.6632	pathogenic	-1.173	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
Y/W	0.7502	likely_pathogenic	0.728	pathogenic	-0.073	Destabilizing	1.0	D	0.774	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.