TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18590	55993;55994;55995	chr2:178601136;178601135;178601134	chr2:179465863;179465862;179465861
N2AB	16949	51070;51071;51072	chr2:178601136;178601135;178601134	chr2:179465863;179465862;179465861
N2A	16022	48289;48290;48291	chr2:178601136;178601135;178601134	chr2:179465863;179465862;179465861
N2B	9525	28798;28799;28800	chr2:178601136;178601135;178601134	chr2:179465863;179465862;179465861
Novex-1	9650	29173;29174;29175	chr2:178601136;178601135;178601134	chr2:179465863;179465862;179465861
Novex-2	9717	29374;29375;29376	chr2:178601136;178601135;178601134	chr2:179465863;179465862;179465861
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: Fn3-23
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.6804
• 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/I	None	None	0.999	N	0.438	0.187	0.376921832658	gnomAD-4.0.0	3.51893E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.17959E-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
L/A	0.2185	likely_benign	0.1868	benign	-1.299	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
L/C	0.4721	ambiguous	0.4349	ambiguous	-0.714	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
L/D	0.4629	ambiguous	0.3721	ambiguous	-0.777	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
L/E	0.2412	likely_benign	0.2014	benign	-0.833	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
L/F	0.1533	likely_benign	0.1255	benign	-1.052	Destabilizing	1.0	D	0.694	prob.neutral	D	0.522596542	None	None	N
L/G	0.4358	ambiguous	0.3459	ambiguous	-1.55	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
L/H	0.2205	likely_benign	0.1796	benign	-0.747	Destabilizing	1.0	D	0.65	neutral	N	0.456142264	None	None	N
L/I	0.0993	likely_benign	0.0951	benign	-0.721	Destabilizing	0.999	D	0.438	neutral	N	0.486118454	None	None	N
L/K	0.1887	likely_benign	0.1641	benign	-0.806	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
L/M	0.1155	likely_benign	0.1046	benign	-0.488	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	N
L/N	0.2344	likely_benign	0.1924	benign	-0.554	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
L/P	0.284	likely_benign	0.2423	benign	-0.881	Destabilizing	1.0	D	0.682	prob.neutral	N	0.492273635	None	None	N
L/Q	0.1362	likely_benign	0.1181	benign	-0.81	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
L/R	0.1757	likely_benign	0.1515	benign	-0.144	Destabilizing	1.0	D	0.688	prob.neutral	N	0.434708199	None	None	N
L/S	0.2483	likely_benign	0.1969	benign	-1.086	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
L/T	0.1825	likely_benign	0.1652	benign	-1.034	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
L/V	0.1013	likely_benign	0.0934	benign	-0.881	Destabilizing	0.999	D	0.489	neutral	N	0.457603701	None	None	N
L/W	0.2888	likely_benign	0.2336	benign	-1.067	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
L/Y	0.3028	likely_benign	0.256	benign	-0.848	Destabilizing	1.0	D	0.715	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.