TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28189	84790;84791;84792	chr2:178561567;178561566;178561565	chr2:179426294;179426293;179426292
N2AB	26548	79867;79868;79869	chr2:178561567;178561566;178561565	chr2:179426294;179426293;179426292
N2A	25621	77086;77087;77088	chr2:178561567;178561566;178561565	chr2:179426294;179426293;179426292
N2B	19124	57595;57596;57597	chr2:178561567;178561566;178561565	chr2:179426294;179426293;179426292
Novex-1	19249	57970;57971;57972	chr2:178561567;178561566;178561565	chr2:179426294;179426293;179426292
Novex-2	19316	58171;58172;58173	chr2:178561567;178561566;178561565	chr2:179426294;179426293;179426292
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: Fn3-93
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.097
• 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	rs1489877895	-1.355	1.0	D	0.887	0.841	0.875450778385	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
Y/C	rs1489877895	-1.355	1.0	D	0.887	0.841	0.875450778385	gnomAD-4.0.0	3.18518E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72027E-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	0.9985	likely_pathogenic	0.9982	pathogenic	-3.806	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/C	0.9253	likely_pathogenic	0.9064	pathogenic	-2.141	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.653048353	None	None	N
Y/D	0.9987	likely_pathogenic	0.9986	pathogenic	-3.979	Highly Destabilizing	1.0	D	0.923	deleterious	D	0.653250157	None	None	N
Y/E	0.9996	likely_pathogenic	0.9995	pathogenic	-3.78	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
Y/F	0.2054	likely_benign	0.1823	benign	-1.689	Destabilizing	0.999	D	0.649	neutral	D	0.557680478	None	None	N
Y/G	0.9939	likely_pathogenic	0.9935	pathogenic	-4.172	Highly Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
Y/H	0.9821	likely_pathogenic	0.9756	pathogenic	-2.786	Highly Destabilizing	1.0	D	0.801	deleterious	D	0.652644744	None	None	N
Y/I	0.9861	likely_pathogenic	0.9823	pathogenic	-2.542	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/K	0.9992	likely_pathogenic	0.9989	pathogenic	-2.783	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
Y/L	0.9721	likely_pathogenic	0.9684	pathogenic	-2.542	Highly Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
Y/M	0.9905	likely_pathogenic	0.9874	pathogenic	-2.177	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
Y/N	0.9861	likely_pathogenic	0.9823	pathogenic	-3.512	Highly Destabilizing	1.0	D	0.915	deleterious	D	0.653048353	None	None	N
Y/P	0.9997	likely_pathogenic	0.9997	pathogenic	-2.984	Highly Destabilizing	1.0	D	0.939	deleterious	None	None	None	None	N
Y/Q	0.9989	likely_pathogenic	0.9984	pathogenic	-3.287	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
Y/R	0.9965	likely_pathogenic	0.9954	pathogenic	-2.444	Highly Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
Y/S	0.9931	likely_pathogenic	0.9912	pathogenic	-3.808	Highly Destabilizing	1.0	D	0.913	deleterious	D	0.653048353	None	None	N
Y/T	0.9981	likely_pathogenic	0.9974	pathogenic	-3.507	Highly Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
Y/V	0.9806	likely_pathogenic	0.9757	pathogenic	-2.984	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
Y/W	0.8419	likely_pathogenic	0.828	pathogenic	-0.92	Destabilizing	1.0	D	0.785	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.