TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21185	63778;63779;63780	chr2:178587756;178587755;178587754	chr2:179452483;179452482;179452481
N2AB	19544	58855;58856;58857	chr2:178587756;178587755;178587754	chr2:179452483;179452482;179452481
N2A	18617	56074;56075;56076	chr2:178587756;178587755;178587754	chr2:179452483;179452482;179452481
N2B	12120	36583;36584;36585	chr2:178587756;178587755;178587754	chr2:179452483;179452482;179452481
Novex-1	12245	36958;36959;36960	chr2:178587756;178587755;178587754	chr2:179452483;179452482;179452481
Novex-2	12312	37159;37160;37161	chr2:178587756;178587755;178587754	chr2:179452483;179452482;179452481
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-123
• Domain position: 9
• Structural Position: 14
• Q(SASA): 0.636
• Predicted PPI site: I

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
I/T	rs794729473	None	None	N	0.093	0.126	0.132336055621	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	6.07533E-05	0
I/V	rs1329536424	None	None	N	0.086	0.11	0.46614307118	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs1329536424	None	None	N	0.086	0.11	0.46614307118	gnomAD-4.0.0	6.57601E-06	None	None	None	None	I	None	2.41266E-05	0	None	0	0	None	0	0	0	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
I/A	0.1381	likely_benign	0.155	benign	-1.304	Destabilizing	None	N	0.093	neutral	None	None	None	None	I
I/C	0.4633	ambiguous	0.5072	ambiguous	-0.955	Destabilizing	0.132	N	0.278	neutral	None	None	None	None	I
I/D	0.535	ambiguous	0.572	pathogenic	-0.878	Destabilizing	0.002	N	0.271	neutral	None	None	None	None	I
I/E	0.4218	ambiguous	0.4554	ambiguous	-0.863	Destabilizing	0.004	N	0.254	neutral	None	None	None	None	I
I/F	0.2012	likely_benign	0.2025	benign	-0.788	Destabilizing	0.021	N	0.219	neutral	None	None	None	None	I
I/G	0.471	ambiguous	0.5361	ambiguous	-1.603	Destabilizing	0.002	N	0.255	neutral	None	None	None	None	I
I/H	0.3147	likely_benign	0.3487	ambiguous	-0.663	Destabilizing	0.132	N	0.411	neutral	None	None	None	None	I
I/K	0.3189	likely_benign	0.3221	benign	-1.05	Destabilizing	0.001	N	0.249	neutral	N	0.458751	None	None	I
I/L	0.1081	likely_benign	0.1159	benign	-0.561	Destabilizing	0.001	N	0.153	neutral	N	0.500888411	None	None	I
I/M	0.0805	likely_benign	0.0869	benign	-0.612	Destabilizing	0.016	N	0.308	neutral	N	0.506256945	None	None	I
I/N	0.1326	likely_benign	0.1444	benign	-1.012	Destabilizing	None	N	0.139	neutral	None	None	None	None	I
I/P	0.4243	ambiguous	0.4981	ambiguous	-0.778	Destabilizing	0.018	N	0.317	neutral	None	None	None	None	I
I/Q	0.2811	likely_benign	0.3076	benign	-1.128	Destabilizing	0.009	N	0.327	neutral	None	None	None	None	I
I/R	0.2757	likely_benign	0.2639	benign	-0.467	Destabilizing	None	N	0.154	neutral	N	0.48286001	None	None	I
I/S	0.1278	likely_benign	0.137	benign	-1.554	Destabilizing	None	N	0.106	neutral	None	None	None	None	I
I/T	0.0585	likely_benign	0.0619	benign	-1.42	Destabilizing	None	N	0.093	neutral	N	0.39050721	None	None	I
I/V	0.0652	likely_benign	0.0711	benign	-0.778	Destabilizing	None	N	0.086	neutral	N	0.415768227	None	None	I
I/W	0.7461	likely_pathogenic	0.7592	pathogenic	-0.873	Destabilizing	0.316	N	0.295	neutral	None	None	None	None	I
I/Y	0.4081	ambiguous	0.3986	ambiguous	-0.648	Destabilizing	0.041	N	0.369	neutral	None	None	None	None	I

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.