TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21507	64744;64745;64746	chr2:178585225;178585224;178585223	chr2:179449952;179449951;179449950
N2AB	19866	59821;59822;59823	chr2:178585225;178585224;178585223	chr2:179449952;179449951;179449950
N2A	18939	57040;57041;57042	chr2:178585225;178585224;178585223	chr2:179449952;179449951;179449950
N2B	12442	37549;37550;37551	chr2:178585225;178585224;178585223	chr2:179449952;179449951;179449950
Novex-1	12567	37924;37925;37926	chr2:178585225;178585224;178585223	chr2:179449952;179449951;179449950
Novex-2	12634	38125;38126;38127	chr2:178585225;178585224;178585223	chr2:179449952;179449951;179449950
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-124
• Domain position: 39
• Structural Position: 58
• Q(SASA): 0.23
• 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
V/F	None	None	0.991	D	0.623	0.37	0.82847125625	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
V/L	None	None	0.76	N	0.406	0.278	0.318540980066	gnomAD-4.0.0	6.00161E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.56251E-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
V/A	0.311	likely_benign	0.2882	benign	-1.637	Destabilizing	0.046	N	0.37	neutral	N	0.497711106	None	None	I
V/C	0.8901	likely_pathogenic	0.8837	pathogenic	-1.152	Destabilizing	0.998	D	0.602	neutral	None	None	None	None	I
V/D	0.8875	likely_pathogenic	0.8308	pathogenic	-1.594	Destabilizing	0.991	D	0.736	prob.delet.	N	0.499232043	None	None	I
V/E	0.809	likely_pathogenic	0.7465	pathogenic	-1.434	Destabilizing	0.986	D	0.674	neutral	None	None	None	None	I
V/F	0.4084	ambiguous	0.3858	ambiguous	-0.958	Destabilizing	0.991	D	0.623	neutral	D	0.527192364	None	None	I
V/G	0.6018	likely_pathogenic	0.5459	ambiguous	-2.114	Highly Destabilizing	0.964	D	0.664	neutral	N	0.49206602	None	None	I
V/H	0.9493	likely_pathogenic	0.9345	pathogenic	-1.721	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	I
V/I	0.0763	likely_benign	0.0774	benign	-0.355	Destabilizing	0.17	N	0.315	neutral	N	0.440685314	None	None	I
V/K	0.9117	likely_pathogenic	0.8778	pathogenic	-1.359	Destabilizing	0.986	D	0.673	neutral	None	None	None	None	I
V/L	0.241	likely_benign	0.225	benign	-0.355	Destabilizing	0.76	D	0.406	neutral	N	0.424558281	None	None	I
V/M	0.2309	likely_benign	0.221	benign	-0.378	Destabilizing	0.993	D	0.541	neutral	None	None	None	None	I
V/N	0.819	likely_pathogenic	0.7691	pathogenic	-1.476	Destabilizing	0.993	D	0.748	deleterious	None	None	None	None	I
V/P	0.785	likely_pathogenic	0.7365	pathogenic	-0.75	Destabilizing	0.993	D	0.689	prob.neutral	None	None	None	None	I
V/Q	0.8747	likely_pathogenic	0.8436	pathogenic	-1.381	Destabilizing	0.993	D	0.707	prob.neutral	None	None	None	None	I
V/R	0.8938	likely_pathogenic	0.8576	pathogenic	-1.164	Destabilizing	0.993	D	0.748	deleterious	None	None	None	None	I
V/S	0.694	likely_pathogenic	0.6473	pathogenic	-2.114	Highly Destabilizing	0.973	D	0.605	neutral	None	None	None	None	I
V/T	0.3892	ambiguous	0.3479	ambiguous	-1.805	Destabilizing	0.953	D	0.446	neutral	None	None	None	None	I
V/W	0.9458	likely_pathogenic	0.9342	pathogenic	-1.334	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	I
V/Y	0.8302	likely_pathogenic	0.7976	pathogenic	-0.942	Destabilizing	0.998	D	0.634	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.