TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26773	80542;80543;80544	chr2:178565815;178565814;178565813	chr2:179430542;179430541;179430540
N2AB	25132	75619;75620;75621	chr2:178565815;178565814;178565813	chr2:179430542;179430541;179430540
N2A	24205	72838;72839;72840	chr2:178565815;178565814;178565813	chr2:179430542;179430541;179430540
N2B	17708	53347;53348;53349	chr2:178565815;178565814;178565813	chr2:179430542;179430541;179430540
Novex-1	17833	53722;53723;53724	chr2:178565815;178565814;178565813	chr2:179430542;179430541;179430540
Novex-2	17900	53923;53924;53925	chr2:178565815;178565814;178565813	chr2:179430542;179430541;179430540
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: Fn3-82
• Domain position: 91
• Structural Position: 125
• Q(SASA): 0.6348
• 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/E	rs1036715959	None	0.012	N	0.155	0.061	0.176091768786	gnomAD-4.0.0	6.84267E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99556E-07	0	0
D/N	None	None	0.682	N	0.605	0.154	0.218845423259	gnomAD-4.0.0	6.84268E-07	None	None	None	None	I	None	0	0	None	0	2.51927E-05	None	0	0	0	0	0
D/Y	None	None	0.979	N	0.78	0.388	0.491248951702	gnomAD-4.0.0	6.84268E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99557E-07	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	0.1446	likely_benign	0.1367	benign	-0.008	Destabilizing	0.518	D	0.6	neutral	N	0.461081527	None	None	I
D/C	0.5525	ambiguous	0.5513	ambiguous	-0.231	Destabilizing	0.996	D	0.8	deleterious	None	None	None	None	I
D/E	0.1054	likely_benign	0.1065	benign	-0.279	Destabilizing	0.012	N	0.155	neutral	N	0.379601491	None	None	I
D/F	0.525	ambiguous	0.5064	ambiguous	-0.048	Destabilizing	0.984	D	0.756	deleterious	None	None	None	None	I
D/G	0.1653	likely_benign	0.1482	benign	-0.121	Destabilizing	0.682	D	0.657	prob.neutral	N	0.508221736	None	None	I
D/H	0.2839	likely_benign	0.2674	benign	0.608	Stabilizing	0.983	D	0.605	neutral	N	0.465969826	None	None	I
D/I	0.3062	likely_benign	0.2937	benign	0.228	Stabilizing	0.953	D	0.788	deleterious	None	None	None	None	I
D/K	0.3747	ambiguous	0.3514	ambiguous	0.371	Stabilizing	0.009	N	0.406	neutral	None	None	None	None	I
D/L	0.3336	likely_benign	0.3241	benign	0.228	Stabilizing	0.909	D	0.686	prob.delet.	None	None	None	None	I
D/M	0.4886	ambiguous	0.4854	ambiguous	-0.014	Destabilizing	0.996	D	0.756	deleterious	None	None	None	None	I
D/N	0.1014	likely_benign	0.0972	benign	0.105	Stabilizing	0.682	D	0.605	neutral	N	0.485806236	None	None	I
D/P	0.7123	likely_pathogenic	0.6831	pathogenic	0.168	Stabilizing	0.953	D	0.613	neutral	None	None	None	None	I
D/Q	0.2983	likely_benign	0.2945	benign	0.115	Stabilizing	0.204	N	0.431	neutral	None	None	None	None	I
D/R	0.4418	ambiguous	0.42	ambiguous	0.648	Stabilizing	0.833	D	0.649	prob.neutral	None	None	None	None	I
D/S	0.1173	likely_benign	0.1108	benign	0.003	Stabilizing	0.74	D	0.502	neutral	None	None	None	None	I
D/T	0.1786	likely_benign	0.1778	benign	0.102	Stabilizing	0.909	D	0.639	neutral	None	None	None	None	I
D/V	0.176	likely_benign	0.1689	benign	0.168	Stabilizing	0.883	D	0.675	prob.neutral	N	0.46394191	None	None	I
D/W	0.8582	likely_pathogenic	0.8552	pathogenic	0.007	Stabilizing	0.996	D	0.785	deleterious	None	None	None	None	I
D/Y	0.2442	likely_benign	0.2284	benign	0.179	Stabilizing	0.979	D	0.78	deleterious	N	0.487833063	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.