TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8069	24430;24431;24432	chr2:178719185;178719184;178719183	chr2:179583912;179583911;179583910
N2AB	7752	23479;23480;23481	chr2:178719185;178719184;178719183	chr2:179583912;179583911;179583910
N2A	6825	20698;20699;20700	chr2:178719185;178719184;178719183	chr2:179583912;179583911;179583910
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-65
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.3911
• 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
S/L	rs751657368	0.15	0.896	N	0.621	0.383	0.59202398213	gnomAD-2.1.1	8.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.98E-06	1.66556E-04
S/L	rs751657368	0.15	0.896	N	0.621	0.383	0.59202398213	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/L	rs751657368	0.15	0.896	N	0.621	0.383	0.59202398213	gnomAD-4.0.0	3.84483E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.39425E-06	0	5.69022E-05

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
S/A	0.0968	likely_benign	0.1033	benign	-0.582	Destabilizing	0.026	N	0.284	neutral	D	0.530288598	None	None	N
S/C	0.1543	likely_benign	0.1645	benign	-0.379	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	N
S/D	0.302	likely_benign	0.3357	benign	-0.109	Destabilizing	0.959	D	0.505	neutral	None	None	None	None	N
S/E	0.3366	likely_benign	0.3803	ambiguous	-0.147	Destabilizing	0.919	D	0.474	neutral	None	None	None	None	N
S/F	0.1768	likely_benign	0.213	benign	-0.855	Destabilizing	0.988	D	0.718	prob.delet.	None	None	None	None	N
S/G	0.0918	likely_benign	0.1028	benign	-0.795	Destabilizing	0.851	D	0.475	neutral	None	None	None	None	N
S/H	0.2078	likely_benign	0.2361	benign	-1.327	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
S/I	0.1685	likely_benign	0.1987	benign	-0.134	Destabilizing	0.976	D	0.706	prob.neutral	None	None	None	None	N
S/K	0.3005	likely_benign	0.3517	ambiguous	-0.686	Destabilizing	0.851	D	0.491	neutral	None	None	None	None	N
S/L	0.1164	likely_benign	0.131	benign	-0.134	Destabilizing	0.896	D	0.621	neutral	N	0.493027072	None	None	N
S/M	0.2166	likely_benign	0.2409	benign	0.169	Stabilizing	0.999	D	0.625	neutral	None	None	None	None	N
S/N	0.1089	likely_benign	0.1211	benign	-0.505	Destabilizing	0.959	D	0.53	neutral	None	None	None	None	N
S/P	0.4796	ambiguous	0.4743	ambiguous	-0.25	Destabilizing	0.984	D	0.623	neutral	N	0.519943191	None	None	N
S/Q	0.283	likely_benign	0.3256	benign	-0.713	Destabilizing	0.988	D	0.529	neutral	None	None	None	None	N
S/R	0.2014	likely_benign	0.2369	benign	-0.54	Destabilizing	0.261	N	0.365	neutral	None	None	None	None	N
S/T	0.0804	likely_benign	0.0834	benign	-0.561	Destabilizing	0.103	N	0.37	neutral	N	0.481206572	None	None	N
S/V	0.189	likely_benign	0.2118	benign	-0.25	Destabilizing	0.851	D	0.643	neutral	None	None	None	None	N
S/W	0.3293	likely_benign	0.3767	ambiguous	-0.826	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
S/Y	0.1716	likely_benign	0.2004	benign	-0.572	Destabilizing	0.996	D	0.721	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.