TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32185	96778;96779;96780	chr2:178543420;178543419;178543418	chr2:179408147;179408146;179408145
N2AB	30544	91855;91856;91857	chr2:178543420;178543419;178543418	chr2:179408147;179408146;179408145
N2A	29617	89074;89075;89076	chr2:178543420;178543419;178543418	chr2:179408147;179408146;179408145
N2B	23120	69583;69584;69585	chr2:178543420;178543419;178543418	chr2:179408147;179408146;179408145
Novex-1	23245	69958;69959;69960	chr2:178543420;178543419;178543418	chr2:179408147;179408146;179408145
Novex-2	23312	70159;70160;70161	chr2:178543420;178543419;178543418	chr2:179408147;179408146;179408145
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: Fn3-122
• Domain position: 81
• Structural Position: 114
• Q(SASA): 0.6663
• 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/H	rs1231801510	0.33	0.998	N	0.697	0.48	0.3571064206	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	1.14784E-04	0	None	0	0	None	0	None	0	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	0.9543	likely_pathogenic	0.948	pathogenic	-0.775	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	I
Y/C	0.4929	ambiguous	0.4277	ambiguous	-0.021	Destabilizing	1.0	D	0.797	deleterious	N	0.500029114	None	None	I
Y/D	0.967	likely_pathogenic	0.9646	pathogenic	0.904	Stabilizing	0.999	D	0.757	deleterious	N	0.491204105	None	None	I
Y/E	0.986	likely_pathogenic	0.9856	pathogenic	0.895	Stabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	I
Y/F	0.1225	likely_benign	0.1085	benign	-0.377	Destabilizing	0.98	D	0.506	neutral	N	0.500933191	None	None	I
Y/G	0.9509	likely_pathogenic	0.9515	pathogenic	-0.971	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	I
Y/H	0.6741	likely_pathogenic	0.6323	pathogenic	0.143	Stabilizing	0.998	D	0.697	prob.neutral	N	0.512630265	None	None	I
Y/I	0.8487	likely_pathogenic	0.8232	pathogenic	-0.272	Destabilizing	0.987	D	0.725	prob.delet.	None	None	None	None	I
Y/K	0.9852	likely_pathogenic	0.9854	pathogenic	0.112	Stabilizing	0.996	D	0.737	prob.delet.	None	None	None	None	I
Y/L	0.7732	likely_pathogenic	0.7523	pathogenic	-0.272	Destabilizing	0.954	D	0.706	prob.neutral	None	None	None	None	I
Y/M	0.9144	likely_pathogenic	0.9053	pathogenic	-0.146	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
Y/N	0.8187	likely_pathogenic	0.8138	pathogenic	-0.111	Destabilizing	0.999	D	0.769	deleterious	N	0.464959549	None	None	I
Y/P	0.9922	likely_pathogenic	0.9918	pathogenic	-0.421	Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	I
Y/Q	0.9662	likely_pathogenic	0.966	pathogenic	-0.048	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	I
Y/R	0.9432	likely_pathogenic	0.9431	pathogenic	0.37	Stabilizing	0.999	D	0.775	deleterious	None	None	None	None	I
Y/S	0.8701	likely_pathogenic	0.863	pathogenic	-0.574	Destabilizing	0.999	D	0.744	deleterious	N	0.521884466	None	None	I
Y/T	0.9556	likely_pathogenic	0.9594	pathogenic	-0.488	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	I
Y/V	0.7997	likely_pathogenic	0.7952	pathogenic	-0.421	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	I
Y/W	0.6017	likely_pathogenic	0.5732	pathogenic	-0.467	Destabilizing	1.0	D	0.688	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.