TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16277	49054;49055;49056	chr2:178614685;178614684;178614683	chr2:179479412;179479411;179479410
N2AB	14636	44131;44132;44133	chr2:178614685;178614684;178614683	chr2:179479412;179479411;179479410
N2A	13709	41350;41351;41352	chr2:178614685;178614684;178614683	chr2:179479412;179479411;179479410
N2B	7212	21859;21860;21861	chr2:178614685;178614684;178614683	chr2:179479412;179479411;179479410
Novex-1	7337	22234;22235;22236	chr2:178614685;178614684;178614683	chr2:179479412;179479411;179479410
Novex-2	7404	22435;22436;22437	chr2:178614685;178614684;178614683	chr2:179479412;179479411;179479410
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-110
• Domain position: 16
• Structural Position: 29
• Q(SASA): 0.2926
• 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	rs1325831010	-0.431	0.999	N	0.593	0.391	0.248417906384	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
E/K	rs1325831010	-0.431	0.999	N	0.593	0.391	0.248417906384	gnomAD-4.0.0	1.59478E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86375E-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	0.2811	likely_benign	0.2985	benign	-0.582	Destabilizing	0.999	D	0.675	prob.neutral	N	0.448265338	None	None	N
E/C	0.8905	likely_pathogenic	0.8968	pathogenic	-0.333	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/D	0.2346	likely_benign	0.2316	benign	-0.837	Destabilizing	0.999	D	0.517	neutral	N	0.451530256	None	None	N
E/F	0.8948	likely_pathogenic	0.8829	pathogenic	0.021	Stabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/G	0.6137	likely_pathogenic	0.6106	pathogenic	-0.913	Destabilizing	1.0	D	0.724	prob.delet.	D	0.590061918	None	None	N
E/H	0.6754	likely_pathogenic	0.6674	pathogenic	-0.013	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/I	0.3376	likely_benign	0.3519	ambiguous	0.307	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/K	0.4668	ambiguous	0.4597	ambiguous	-0.109	Destabilizing	0.999	D	0.593	neutral	N	0.447711249	None	None	N
E/L	0.5509	ambiguous	0.5723	pathogenic	0.307	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/M	0.5583	ambiguous	0.5788	pathogenic	0.493	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/N	0.4435	ambiguous	0.4443	ambiguous	-0.719	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
E/P	0.9654	likely_pathogenic	0.9699	pathogenic	0.033	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/Q	0.2235	likely_benign	0.2326	benign	-0.585	Destabilizing	1.0	D	0.643	neutral	N	0.452573599	None	None	N
E/R	0.641	likely_pathogenic	0.6218	pathogenic	0.211	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/S	0.3273	likely_benign	0.3379	benign	-0.928	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
E/T	0.2328	likely_benign	0.2445	benign	-0.644	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
E/V	0.1928	likely_benign	0.2093	benign	0.033	Stabilizing	1.0	D	0.747	deleterious	N	0.429320485	None	None	N
E/W	0.982	likely_pathogenic	0.9778	pathogenic	0.301	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/Y	0.8604	likely_pathogenic	0.8362	pathogenic	0.297	Stabilizing	1.0	D	0.778	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.