TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20825	62698;62699;62700	chr2:178589252;178589251;178589250	chr2:179453979;179453978;179453977
N2AB	19184	57775;57776;57777	chr2:178589252;178589251;178589250	chr2:179453979;179453978;179453977
N2A	18257	54994;54995;54996	chr2:178589252;178589251;178589250	chr2:179453979;179453978;179453977
N2B	11760	35503;35504;35505	chr2:178589252;178589251;178589250	chr2:179453979;179453978;179453977
Novex-1	11885	35878;35879;35880	chr2:178589252;178589251;178589250	chr2:179453979;179453978;179453977
Novex-2	11952	36079;36080;36081	chr2:178589252;178589251;178589250	chr2:179453979;179453978;179453977
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-122
• Domain position: 57
• Structural Position: 134
• Q(SASA): 0.4778
• 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
D/N	None	None	0.83	N	0.735	0.216	0.44349138644	gnomAD-4.0.0	6.84326E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65695E-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
D/A	0.199	likely_benign	0.3039	benign	-0.124	Destabilizing	0.41	N	0.682	prob.neutral	N	0.502427206	None	None	N
D/C	0.6935	likely_pathogenic	0.8025	pathogenic	0.082	Stabilizing	0.993	D	0.724	prob.delet.	None	None	None	None	N
D/E	0.1076	likely_benign	0.1992	benign	-0.229	Destabilizing	0.004	N	0.246	neutral	N	0.463716889	None	None	N
D/F	0.596	likely_pathogenic	0.7148	pathogenic	-0.106	Destabilizing	0.993	D	0.753	deleterious	None	None	None	None	N
D/G	0.1725	likely_benign	0.2352	benign	-0.278	Destabilizing	0.581	D	0.66	neutral	N	0.41946468	None	None	N
D/H	0.38	ambiguous	0.5005	ambiguous	0.216	Stabilizing	0.974	D	0.717	prob.delet.	N	0.488556847	None	None	N
D/I	0.4113	ambiguous	0.5637	ambiguous	0.223	Stabilizing	0.929	D	0.762	deleterious	None	None	None	None	N
D/K	0.4603	ambiguous	0.655	pathogenic	0.586	Stabilizing	0.764	D	0.689	prob.neutral	None	None	None	None	N
D/L	0.4314	ambiguous	0.5862	pathogenic	0.223	Stabilizing	0.866	D	0.759	deleterious	None	None	None	None	N
D/M	0.6065	likely_pathogenic	0.7435	pathogenic	0.242	Stabilizing	0.993	D	0.739	prob.delet.	None	None	None	None	N
D/N	0.1189	likely_benign	0.135	benign	0.217	Stabilizing	0.83	D	0.735	prob.delet.	N	0.470893578	None	None	N
D/P	0.7492	likely_pathogenic	0.8696	pathogenic	0.128	Stabilizing	0.929	D	0.741	deleterious	None	None	None	None	N
D/Q	0.3433	ambiguous	0.5222	ambiguous	0.247	Stabilizing	0.764	D	0.781	deleterious	None	None	None	None	N
D/R	0.525	ambiguous	0.6816	pathogenic	0.705	Stabilizing	0.764	D	0.751	deleterious	None	None	None	None	N
D/S	0.1451	likely_benign	0.1914	benign	0.161	Stabilizing	0.48	N	0.677	prob.neutral	None	None	None	None	N
D/T	0.2273	likely_benign	0.3231	benign	0.292	Stabilizing	0.866	D	0.687	prob.neutral	None	None	None	None	N
D/V	0.2736	likely_benign	0.392	ambiguous	0.128	Stabilizing	0.83	D	0.758	deleterious	N	0.518340808	None	None	N
D/W	0.8911	likely_pathogenic	0.9382	pathogenic	-0.001	Destabilizing	0.993	D	0.733	prob.delet.	None	None	None	None	N
D/Y	0.3443	ambiguous	0.4118	ambiguous	0.136	Stabilizing	0.991	D	0.753	deleterious	N	0.49184764	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.