TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22434	67525;67526;67527	chr2:178579987;178579986;178579985	chr2:179444714;179444713;179444712
N2AB	20793	62602;62603;62604	chr2:178579987;178579986;178579985	chr2:179444714;179444713;179444712
N2A	19866	59821;59822;59823	chr2:178579987;178579986;178579985	chr2:179444714;179444713;179444712
N2B	13369	40330;40331;40332	chr2:178579987;178579986;178579985	chr2:179444714;179444713;179444712
Novex-1	13494	40705;40706;40707	chr2:178579987;178579986;178579985	chr2:179444714;179444713;179444712
Novex-2	13561	40906;40907;40908	chr2:178579987;178579986;178579985	chr2:179444714;179444713;179444712
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: Fn3-50
• Domain position: 81
• Structural Position: 114
• Q(SASA): 0.6125
• 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
Y/N	rs1553623044	None	1.0	N	0.767	0.509	0.364926071151	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/N	rs1553623044	None	1.0	N	0.767	0.509	0.364926071151	gnomAD-4.0.0	2.56399E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.78923E-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	0.9257	likely_pathogenic	0.9297	pathogenic	-0.878	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
Y/C	0.5667	likely_pathogenic	0.6406	pathogenic	0.018	Stabilizing	1.0	D	0.795	deleterious	N	0.470861806	None	None	I
Y/D	0.9206	likely_pathogenic	0.9387	pathogenic	0.885	Stabilizing	1.0	D	0.752	deleterious	N	0.497787471	None	None	I
Y/E	0.9707	likely_pathogenic	0.9772	pathogenic	0.866	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
Y/F	0.1238	likely_benign	0.1284	benign	-0.505	Destabilizing	0.999	D	0.49	neutral	N	0.472111794	None	None	I
Y/G	0.9353	likely_pathogenic	0.9361	pathogenic	-1.068	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
Y/H	0.6809	likely_pathogenic	0.7307	pathogenic	0.128	Stabilizing	1.0	D	0.695	prob.neutral	N	0.472556872	None	None	I
Y/I	0.6673	likely_pathogenic	0.7288	pathogenic	-0.401	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
Y/K	0.9571	likely_pathogenic	0.9703	pathogenic	0.143	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
Y/L	0.7554	likely_pathogenic	0.7826	pathogenic	-0.401	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	I
Y/M	0.8195	likely_pathogenic	0.8467	pathogenic	-0.141	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
Y/N	0.6463	likely_pathogenic	0.6841	pathogenic	-0.029	Destabilizing	1.0	D	0.767	deleterious	N	0.519478879	None	None	I
Y/P	0.9962	likely_pathogenic	0.9965	pathogenic	-0.541	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
Y/Q	0.9448	likely_pathogenic	0.9591	pathogenic	-0.029	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
Y/R	0.9259	likely_pathogenic	0.9438	pathogenic	0.497	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
Y/S	0.8719	likely_pathogenic	0.8948	pathogenic	-0.522	Destabilizing	1.0	D	0.743	deleterious	N	0.476088818	None	None	I
Y/T	0.9301	likely_pathogenic	0.9439	pathogenic	-0.452	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
Y/V	0.6659	likely_pathogenic	0.7195	pathogenic	-0.541	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
Y/W	0.7041	likely_pathogenic	0.7279	pathogenic	-0.563	Destabilizing	1.0	D	0.687	prob.neutral	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.