TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1907	5944;5945;5946	chr2:178776145;178776144;178776143	chr2:179640872;179640871;179640870
N2AB	1907	5944;5945;5946	chr2:178776145;178776144;178776143	chr2:179640872;179640871;179640870
N2A	1907	5944;5945;5946	chr2:178776145;178776144;178776143	chr2:179640872;179640871;179640870
N2B	1861	5806;5807;5808	chr2:178776145;178776144;178776143	chr2:179640872;179640871;179640870
Novex-1	1861	5806;5807;5808	chr2:178776145;178776144;178776143	chr2:179640872;179640871;179640870
Novex-2	1861	5806;5807;5808	chr2:178776145;178776144;178776143	chr2:179640872;179640871;179640870
Novex-3	1907	5944;5945;5946	chr2:178776145;178776144;178776143	chr2:179640872;179640871;179640870

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-9
• Domain position: 67
• Structural Position: 151
• Q(SASA): 0.3743
• 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	None	None	0.984	N	0.623	0.425	0.463672176093	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1131	likely_benign	0.1037	benign	-0.741	Destabilizing	0.64	D	0.439	neutral	N	0.374403615	None	None	N
T/C	0.5805	likely_pathogenic	0.5428	ambiguous	-0.401	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
T/D	0.7663	likely_pathogenic	0.6969	pathogenic	0.25	Stabilizing	0.919	D	0.573	neutral	None	None	None	None	N
T/E	0.5733	likely_pathogenic	0.5147	ambiguous	0.228	Stabilizing	0.919	D	0.575	neutral	None	None	None	None	N
T/F	0.6094	likely_pathogenic	0.4876	ambiguous	-0.924	Destabilizing	0.996	D	0.733	prob.delet.	None	None	None	None	N
T/G	0.3226	likely_benign	0.3106	benign	-0.964	Destabilizing	0.851	D	0.618	neutral	None	None	None	None	N
T/H	0.5321	ambiguous	0.4832	ambiguous	-1.24	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	N
T/I	0.5084	ambiguous	0.3942	ambiguous	-0.248	Destabilizing	0.984	D	0.623	neutral	N	0.506025056	None	None	N
T/K	0.464	ambiguous	0.4091	ambiguous	-0.501	Destabilizing	0.896	D	0.571	neutral	N	0.482123677	None	None	N
T/L	0.2545	likely_benign	0.1923	benign	-0.248	Destabilizing	0.919	D	0.558	neutral	None	None	None	None	N
T/M	0.157	likely_benign	0.1285	benign	0.031	Stabilizing	0.999	D	0.667	neutral	None	None	None	None	N
T/N	0.2688	likely_benign	0.2213	benign	-0.346	Destabilizing	0.919	D	0.481	neutral	None	None	None	None	N
T/P	0.7626	likely_pathogenic	0.7921	pathogenic	-0.381	Destabilizing	0.984	D	0.62	neutral	N	0.512068058	None	None	N
T/Q	0.4178	ambiguous	0.3775	ambiguous	-0.541	Destabilizing	0.988	D	0.666	neutral	None	None	None	None	N
T/R	0.4035	ambiguous	0.3522	ambiguous	-0.291	Destabilizing	0.968	D	0.657	neutral	N	0.481406714	None	None	N
T/S	0.1289	likely_benign	0.1217	benign	-0.694	Destabilizing	0.046	N	0.183	neutral	N	0.389203819	None	None	N
T/V	0.3295	likely_benign	0.2639	benign	-0.381	Destabilizing	0.919	D	0.461	neutral	None	None	None	None	N
T/W	0.9005	likely_pathogenic	0.8589	pathogenic	-0.828	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
T/Y	0.6653	likely_pathogenic	0.5683	pathogenic	-0.592	Destabilizing	0.996	D	0.735	prob.delet.	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.