TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2555	7888;7889;7890	chr2:178773301;178773300;178773299	chr2:179638028;179638027;179638026
N2AB	2555	7888;7889;7890	chr2:178773301;178773300;178773299	chr2:179638028;179638027;179638026
N2A	2555	7888;7889;7890	chr2:178773301;178773300;178773299	chr2:179638028;179638027;179638026
N2B	2509	7750;7751;7752	chr2:178773301;178773300;178773299	chr2:179638028;179638027;179638026
Novex-1	2509	7750;7751;7752	chr2:178773301;178773300;178773299	chr2:179638028;179638027;179638026
Novex-2	2509	7750;7751;7752	chr2:178773301;178773300;178773299	chr2:179638028;179638027;179638026
Novex-3	2555	7888;7889;7890	chr2:178773301;178773300;178773299	chr2:179638028;179638027;179638026

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-15
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.1837
• 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
E/K	None	None	0.999	D	0.471	0.455	0.389439708392	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
E/A	0.4977	ambiguous	0.456	ambiguous	-1.116	Destabilizing	0.999	D	0.626	neutral	D	0.600665588	None	None	N
E/C	0.9644	likely_pathogenic	0.9633	pathogenic	-0.668	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/D	0.7544	likely_pathogenic	0.7	pathogenic	-1.402	Destabilizing	0.999	D	0.429	neutral	D	0.600800251	None	None	N
E/F	0.952	likely_pathogenic	0.9425	pathogenic	-0.569	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
E/G	0.7815	likely_pathogenic	0.7428	pathogenic	-1.521	Destabilizing	1.0	D	0.746	deleterious	D	0.682445765	None	None	N
E/H	0.8898	likely_pathogenic	0.8756	pathogenic	-0.774	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
E/I	0.6988	likely_pathogenic	0.661	pathogenic	0.017	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/K	0.6756	likely_pathogenic	0.6246	pathogenic	-1.009	Destabilizing	0.999	D	0.471	neutral	D	0.530483018	None	None	N
E/L	0.8147	likely_pathogenic	0.7875	pathogenic	0.017	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/M	0.7764	likely_pathogenic	0.7513	pathogenic	0.576	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/N	0.8463	likely_pathogenic	0.8047	pathogenic	-1.418	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/P	0.9917	likely_pathogenic	0.9933	pathogenic	-0.341	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
E/Q	0.3695	ambiguous	0.3446	ambiguous	-1.245	Destabilizing	1.0	D	0.574	neutral	N	0.50574142	None	None	N
E/R	0.7998	likely_pathogenic	0.7783	pathogenic	-0.761	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
E/S	0.6777	likely_pathogenic	0.6252	pathogenic	-1.911	Destabilizing	0.999	D	0.523	neutral	None	None	None	None	N
E/T	0.6546	likely_pathogenic	0.6127	pathogenic	-1.556	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/V	0.5131	ambiguous	0.4678	ambiguous	-0.341	Destabilizing	1.0	D	0.779	deleterious	D	0.561551833	None	None	N
E/W	0.9899	likely_pathogenic	0.9891	pathogenic	-0.394	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
E/Y	0.9346	likely_pathogenic	0.927	pathogenic	-0.31	Destabilizing	1.0	D	0.793	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.