TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5121	15586;15587;15588	chr2:178734463;178734462;178734461	chr2:179599190;179599189;179599188
N2AB	4804	14635;14636;14637	chr2:178734463;178734462;178734461	chr2:179599190;179599189;179599188
N2A	3877	11854;11855;11856	chr2:178734463;178734462;178734461	chr2:179599190;179599189;179599188
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: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-34
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.143
• 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/H	rs2081084380	None	1.0	N	0.727	0.461	0.508696012846	gnomAD-4.0.0	3.18298E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71729E-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	0.9507	likely_pathogenic	0.9683	pathogenic	-2.538	Highly Destabilizing	0.998	D	0.653	neutral	None	None	None	None	N
Y/C	0.4952	ambiguous	0.6587	pathogenic	-1.752	Destabilizing	1.0	D	0.781	deleterious	D	0.65688535	None	None	N
Y/D	0.9689	likely_pathogenic	0.9771	pathogenic	-1.837	Destabilizing	1.0	D	0.814	deleterious	D	0.703879385	None	None	N
Y/E	0.9811	likely_pathogenic	0.9859	pathogenic	-1.641	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
Y/F	0.1803	likely_benign	0.203	benign	-0.867	Destabilizing	0.434	N	0.291	neutral	N	0.50766468	None	None	N
Y/G	0.9291	likely_pathogenic	0.953	pathogenic	-2.958	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
Y/H	0.6524	likely_pathogenic	0.676	pathogenic	-1.51	Destabilizing	1.0	D	0.727	prob.delet.	N	0.510880949	None	None	N
Y/I	0.8066	likely_pathogenic	0.8574	pathogenic	-1.191	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
Y/K	0.9808	likely_pathogenic	0.9862	pathogenic	-1.817	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
Y/L	0.7918	likely_pathogenic	0.8386	pathogenic	-1.191	Destabilizing	0.994	D	0.509	neutral	None	None	None	None	N
Y/M	0.8824	likely_pathogenic	0.9191	pathogenic	-1.107	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
Y/N	0.7581	likely_pathogenic	0.7886	pathogenic	-2.484	Highly Destabilizing	1.0	D	0.803	deleterious	D	0.68816977	None	None	N
Y/P	0.9965	likely_pathogenic	0.9977	pathogenic	-1.647	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
Y/Q	0.9464	likely_pathogenic	0.962	pathogenic	-2.185	Highly Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
Y/R	0.9491	likely_pathogenic	0.9625	pathogenic	-1.663	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
Y/S	0.8703	likely_pathogenic	0.9085	pathogenic	-3.051	Highly Destabilizing	1.0	D	0.774	deleterious	D	0.629259041	None	None	N
Y/T	0.9288	likely_pathogenic	0.9521	pathogenic	-2.73	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
Y/V	0.7522	likely_pathogenic	0.8085	pathogenic	-1.647	Destabilizing	0.997	D	0.637	neutral	None	None	None	None	N
Y/W	0.7366	likely_pathogenic	0.7885	pathogenic	-0.241	Destabilizing	1.0	D	0.706	prob.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.