TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5900	17923;17924;17925	chr2:178730967;178730966;178730965	chr2:179595694;179595693;179595692
N2AB	5583	16972;16973;16974	chr2:178730967;178730966;178730965	chr2:179595694;179595693;179595692
N2A	4656	14191;14192;14193	chr2:178730967;178730966;178730965	chr2:179595694;179595693;179595692
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-42
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.9537
• 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
D/Y	None	None	1.0	N	0.718	0.512	0.78712903431	gnomAD-4.0.0	6.00162E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.56252E-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
D/A	0.1691	likely_benign	0.1996	benign	-0.048	Destabilizing	0.999	D	0.565	neutral	N	0.479897063	None	None	I
D/C	0.7157	likely_pathogenic	0.7559	pathogenic	0.176	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
D/E	0.1567	likely_benign	0.1946	benign	-0.271	Destabilizing	0.767	D	0.37	neutral	N	0.454651902	None	None	I
D/F	0.6611	likely_pathogenic	0.7196	pathogenic	-0.228	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
D/G	0.2148	likely_benign	0.2448	benign	-0.173	Destabilizing	0.998	D	0.579	neutral	N	0.498637539	None	None	I
D/H	0.3421	ambiguous	0.3899	ambiguous	0.093	Stabilizing	1.0	D	0.665	neutral	D	0.530403241	None	None	I
D/I	0.3744	ambiguous	0.428	ambiguous	0.213	Stabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
D/K	0.4235	ambiguous	0.481	ambiguous	0.539	Stabilizing	0.999	D	0.606	neutral	None	None	None	None	I
D/L	0.4321	ambiguous	0.4845	ambiguous	0.213	Stabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
D/M	0.6277	likely_pathogenic	0.6841	pathogenic	0.246	Stabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
D/N	0.1182	likely_benign	0.1308	benign	0.385	Stabilizing	0.999	D	0.637	neutral	N	0.513990994	None	None	I
D/P	0.6099	likely_pathogenic	0.663	pathogenic	0.146	Stabilizing	1.0	D	0.645	neutral	None	None	None	None	I
D/Q	0.3929	ambiguous	0.4593	ambiguous	0.37	Stabilizing	0.999	D	0.672	neutral	None	None	None	None	I
D/R	0.4542	ambiguous	0.517	ambiguous	0.624	Stabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	I
D/S	0.138	likely_benign	0.1547	benign	0.294	Stabilizing	0.997	D	0.572	neutral	None	None	None	None	I
D/T	0.2468	likely_benign	0.2827	benign	0.388	Stabilizing	1.0	D	0.632	neutral	None	None	None	None	I
D/V	0.2226	likely_benign	0.2614	benign	0.146	Stabilizing	0.999	D	0.693	prob.neutral	D	0.525554782	None	None	I
D/W	0.914	likely_pathogenic	0.9338	pathogenic	-0.195	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
D/Y	0.3122	likely_benign	0.3553	ambiguous	-0.005	Destabilizing	1.0	D	0.718	prob.delet.	N	0.494277612	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.