TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25097	75514;75515;75516	chr2:178570843;178570842;178570841	chr2:179435570;179435569;179435568
N2AB	23456	70591;70592;70593	chr2:178570843;178570842;178570841	chr2:179435570;179435569;179435568
N2A	22529	67810;67811;67812	chr2:178570843;178570842;178570841	chr2:179435570;179435569;179435568
N2B	16032	48319;48320;48321	chr2:178570843;178570842;178570841	chr2:179435570;179435569;179435568
Novex-1	16157	48694;48695;48696	chr2:178570843;178570842;178570841	chr2:179435570;179435569;179435568
Novex-2	16224	48895;48896;48897	chr2:178570843;178570842;178570841	chr2:179435570;179435569;179435568
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-70
• Domain position: 92
• Structural Position: 124
• Q(SASA): 0.2034
• 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
T/I	rs777052871	-0.14	0.015	N	0.549	0.284	0.167679373172	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
T/I	rs777052871	-0.14	0.015	N	0.549	0.284	0.167679373172	gnomAD-4.0.0	1.59175E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85925E-06	0	0
T/K	None	None	0.883	N	0.792	0.394	0.214338557667	gnomAD-4.0.0	1.59175E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85925E-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
T/A	0.2195	likely_benign	0.2733	benign	-1.184	Destabilizing	0.007	N	0.403	neutral	N	0.461929404	None	None	N
T/C	0.6643	likely_pathogenic	0.719	pathogenic	-0.909	Destabilizing	0.987	D	0.726	deleterious	None	None	None	None	N
T/D	0.9399	likely_pathogenic	0.9361	pathogenic	-1.082	Destabilizing	0.909	D	0.82	deleterious	None	None	None	None	N
T/E	0.9419	likely_pathogenic	0.9429	pathogenic	-0.932	Destabilizing	0.909	D	0.797	deleterious	None	None	None	None	N
T/F	0.9354	likely_pathogenic	0.9412	pathogenic	-0.889	Destabilizing	0.909	D	0.773	deleterious	None	None	None	None	N
T/G	0.569	likely_pathogenic	0.6168	pathogenic	-1.581	Destabilizing	0.587	D	0.747	deleterious	None	None	None	None	N
T/H	0.923	likely_pathogenic	0.9244	pathogenic	-1.694	Destabilizing	0.996	D	0.73	deleterious	None	None	None	None	N
T/I	0.8546	likely_pathogenic	0.8587	pathogenic	-0.162	Destabilizing	0.015	N	0.549	neutral	N	0.460408466	None	None	N
T/K	0.9455	likely_pathogenic	0.9451	pathogenic	-0.722	Destabilizing	0.883	D	0.792	deleterious	N	0.483111532	None	None	N
T/L	0.5855	likely_pathogenic	0.613	pathogenic	-0.162	Destabilizing	0.329	N	0.753	deleterious	None	None	None	None	N
T/M	0.4466	ambiguous	0.4533	ambiguous	-0.08	Destabilizing	0.974	D	0.737	deleterious	None	None	None	None	N
T/N	0.7405	likely_pathogenic	0.7326	pathogenic	-1.205	Destabilizing	0.909	D	0.783	deleterious	None	None	None	None	N
T/P	0.7212	likely_pathogenic	0.7323	pathogenic	-0.47	Destabilizing	0.938	D	0.803	deleterious	N	0.458779533	None	None	N
T/Q	0.9048	likely_pathogenic	0.9077	pathogenic	-1.102	Destabilizing	0.953	D	0.789	deleterious	None	None	None	None	N
T/R	0.9201	likely_pathogenic	0.923	pathogenic	-0.769	Destabilizing	0.883	D	0.809	deleterious	N	0.489948387	None	None	N
T/S	0.1451	likely_benign	0.1581	benign	-1.502	Destabilizing	0.028	N	0.505	neutral	N	0.410876042	None	None	N
T/V	0.6145	likely_pathogenic	0.6456	pathogenic	-0.47	Destabilizing	0.168	N	0.696	prob.delet.	None	None	None	None	N
T/W	0.9827	likely_pathogenic	0.9828	pathogenic	-0.913	Destabilizing	0.996	D	0.757	deleterious	None	None	None	None	N
T/Y	0.9434	likely_pathogenic	0.9474	pathogenic	-0.598	Destabilizing	0.953	D	0.756	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.