TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4008	12247;12248;12249	chr2:178741211;178741210;178741209	chr2:179605938;179605937;179605936
N2AB	3691	11296;11297;11298	chr2:178741211;178741210;178741209	chr2:179605938;179605937;179605936
N2A	None	None	chr2:None	chr2:None
N2B	3645	11158;11159;11160	chr2:178741211;178741210;178741209	chr2:179605938;179605937;179605936
Novex-1	3770	11533;11534;11535	chr2:178741211;178741210;178741209	chr2:179605938;179605937;179605936
Novex-2	3837	11734;11735;11736	chr2:178741211;178741210;178741209	chr2:179605938;179605937;179605936
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-28
• Domain position: 71
• Structural Position: 153
• Q(SASA): 0.433
• 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
L/H	None	None	0.003	D	0.418	0.268	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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
L/A	0.2494	likely_benign	0.2087	benign	-1.476	Destabilizing	0.116	N	0.469	neutral	None	None	None	None	N
L/C	0.3437	ambiguous	0.3335	benign	-0.822	Destabilizing	0.981	D	0.553	neutral	None	None	None	None	N
L/D	0.4876	ambiguous	0.4187	ambiguous	-0.658	Destabilizing	0.69	D	0.592	neutral	None	None	None	None	N
L/E	0.267	likely_benign	0.2282	benign	-0.645	Destabilizing	0.388	N	0.576	neutral	None	None	None	None	N
L/F	0.1084	likely_benign	0.1017	benign	-0.936	Destabilizing	0.003	N	0.271	neutral	N	0.507624979	None	None	N
L/G	0.4546	ambiguous	0.3927	ambiguous	-1.802	Destabilizing	0.241	N	0.554	neutral	None	None	None	None	N
L/H	0.1546	likely_benign	0.1443	benign	-0.955	Destabilizing	0.003	N	0.418	neutral	D	0.528796776	None	None	N
L/I	0.0775	likely_benign	0.0766	benign	-0.657	Destabilizing	0.001	N	0.299	neutral	N	0.487322256	None	None	N
L/K	0.1857	likely_benign	0.1638	benign	-0.925	Destabilizing	0.388	N	0.577	neutral	None	None	None	None	N
L/M	0.1264	likely_benign	0.1076	benign	-0.547	Destabilizing	0.054	N	0.279	neutral	None	None	None	None	N
L/N	0.2729	likely_benign	0.2321	benign	-0.724	Destabilizing	0.527	D	0.591	neutral	None	None	None	None	N
L/P	0.286	likely_benign	0.2264	benign	-0.898	Destabilizing	0.773	D	0.594	neutral	D	0.607571493	None	None	N
L/Q	0.1313	likely_benign	0.1211	benign	-0.864	Destabilizing	0.69	D	0.593	neutral	None	None	None	None	N
L/R	0.1175	likely_benign	0.1146	benign	-0.386	Destabilizing	0.627	D	0.594	neutral	N	0.502259741	None	None	N
L/S	0.2254	likely_benign	0.1871	benign	-1.369	Destabilizing	0.008	N	0.396	neutral	None	None	None	None	N
L/T	0.1824	likely_benign	0.1552	benign	-1.235	Destabilizing	0.241	N	0.463	neutral	None	None	None	None	N
L/V	0.0897	likely_benign	0.0852	benign	-0.898	Destabilizing	0.033	N	0.479	neutral	N	0.487148192	None	None	N
L/W	0.1795	likely_benign	0.1708	benign	-1.0	Destabilizing	0.981	D	0.573	neutral	None	None	None	None	N
L/Y	0.2363	likely_benign	0.2165	benign	-0.776	Destabilizing	0.527	D	0.579	neutral	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.