TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23849	71770;71771;71772	chr2:178574587;178574586;178574585	chr2:179439314;179439313;179439312
N2AB	22208	66847;66848;66849	chr2:178574587;178574586;178574585	chr2:179439314;179439313;179439312
N2A	21281	64066;64067;64068	chr2:178574587;178574586;178574585	chr2:179439314;179439313;179439312
N2B	14784	44575;44576;44577	chr2:178574587;178574586;178574585	chr2:179439314;179439313;179439312
Novex-1	14909	44950;44951;44952	chr2:178574587;178574586;178574585	chr2:179439314;179439313;179439312
Novex-2	14976	45151;45152;45153	chr2:178574587;178574586;178574585	chr2:179439314;179439313;179439312
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-61
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.5356
• 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
E/K	None	None	0.999	N	0.609	0.396	0.361160317528	gnomAD-4.0.0	1.59194E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8595E-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
E/A	0.1528	likely_benign	0.174	benign	-0.316	Destabilizing	0.999	D	0.743	deleterious	N	0.406636163	None	None	I
E/C	0.8107	likely_pathogenic	0.8442	pathogenic	-0.424	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
E/D	0.2451	likely_benign	0.2829	benign	-1.009	Destabilizing	0.999	D	0.526	neutral	N	0.474357752	None	None	I
E/F	0.8169	likely_pathogenic	0.8399	pathogenic	0.408	Stabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
E/G	0.2449	likely_benign	0.2822	benign	-0.663	Destabilizing	1.0	D	0.769	deleterious	N	0.501626624	None	None	I
E/H	0.5207	ambiguous	0.585	pathogenic	0.459	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	I
E/I	0.3191	likely_benign	0.3712	ambiguous	0.622	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
E/K	0.1157	likely_benign	0.1335	benign	-0.235	Destabilizing	0.999	D	0.609	neutral	N	0.450563086	None	None	I
E/L	0.379	ambiguous	0.4321	ambiguous	0.622	Stabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
E/M	0.4372	ambiguous	0.4768	ambiguous	0.648	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
E/N	0.405	ambiguous	0.4684	ambiguous	-0.845	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
E/P	0.3444	ambiguous	0.404	ambiguous	0.331	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
E/Q	0.1216	likely_benign	0.1341	benign	-0.665	Destabilizing	1.0	D	0.663	neutral	N	0.487619964	None	None	I
E/R	0.2285	likely_benign	0.255	benign	0.167	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
E/S	0.2609	likely_benign	0.2977	benign	-1.077	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	I
E/T	0.2597	likely_benign	0.3005	benign	-0.77	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
E/V	0.2007	likely_benign	0.2345	benign	0.331	Stabilizing	1.0	D	0.806	deleterious	N	0.494988654	None	None	I
E/W	0.9512	likely_pathogenic	0.9582	pathogenic	0.634	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
E/Y	0.6837	likely_pathogenic	0.7096	pathogenic	0.67	Stabilizing	1.0	D	0.782	deleterious	None	None	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.