TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23525	70798;70799;70800	chr2:178575559;178575558;178575557	chr2:179440286;179440285;179440284
N2AB	21884	65875;65876;65877	chr2:178575559;178575558;178575557	chr2:179440286;179440285;179440284
N2A	20957	63094;63095;63096	chr2:178575559;178575558;178575557	chr2:179440286;179440285;179440284
N2B	14460	43603;43604;43605	chr2:178575559;178575558;178575557	chr2:179440286;179440285;179440284
Novex-1	14585	43978;43979;43980	chr2:178575559;178575558;178575557	chr2:179440286;179440285;179440284
Novex-2	14652	44179;44180;44181	chr2:178575559;178575558;178575557	chr2:179440286;179440285;179440284
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: Fn3-58
• Domain position: 91
• Structural Position: 125
• Q(SASA): 0.6194
• 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
E/G	rs1709774465	None	0.521	N	0.522	0.334	0.391775403332	gnomAD-4.0.0	1.59151E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85914E-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	0.1481	likely_benign	0.162	benign	-0.145	Destabilizing	0.14	N	0.463	neutral	N	0.474110127	None	None	N
E/C	0.7898	likely_pathogenic	0.8194	pathogenic	-0.325	Destabilizing	0.972	D	0.768	deleterious	None	None	None	None	N
E/D	0.0896	likely_benign	0.0955	benign	-0.308	Destabilizing	None	N	0.157	neutral	N	0.447154634	None	None	N
E/F	0.6573	likely_pathogenic	0.699	pathogenic	0.016	Stabilizing	0.946	D	0.751	deleterious	None	None	None	None	N
E/G	0.1747	likely_benign	0.2042	benign	-0.303	Destabilizing	0.521	D	0.522	neutral	N	0.47636508	None	None	N
E/H	0.4588	ambiguous	0.5161	ambiguous	0.636	Stabilizing	0.939	D	0.509	neutral	None	None	None	None	N
E/I	0.2705	likely_benign	0.2961	benign	0.226	Stabilizing	0.728	D	0.791	deleterious	None	None	None	None	N
E/K	0.1889	likely_benign	0.2293	benign	0.359	Stabilizing	0.002	N	0.305	neutral	N	0.468767756	None	None	N
E/L	0.3313	likely_benign	0.3667	ambiguous	0.226	Stabilizing	0.568	D	0.688	prob.delet.	None	None	None	None	N
E/M	0.3713	ambiguous	0.4012	ambiguous	-0.026	Destabilizing	0.846	D	0.693	prob.delet.	None	None	None	None	N
E/N	0.2047	likely_benign	0.2309	benign	-0.076	Destabilizing	0.149	N	0.476	neutral	None	None	None	None	N
E/P	0.8298	likely_pathogenic	0.8851	pathogenic	0.121	Stabilizing	0.284	N	0.54	neutral	None	None	None	None	N
E/Q	0.1506	likely_benign	0.1687	benign	-0.019	Destabilizing	0.302	N	0.489	neutral	N	0.478744936	None	None	N
E/R	0.3294	likely_benign	0.4024	ambiguous	0.692	Stabilizing	0.585	D	0.465	neutral	None	None	None	None	N
E/S	0.1712	likely_benign	0.1863	benign	-0.198	Destabilizing	0.302	N	0.376	neutral	None	None	None	None	N
E/T	0.1724	likely_benign	0.1873	benign	-0.053	Destabilizing	0.677	D	0.489	neutral	None	None	None	None	N
E/V	0.1686	likely_benign	0.1863	benign	0.121	Stabilizing	0.414	N	0.618	neutral	N	0.49128933	None	None	N
E/W	0.8878	likely_pathogenic	0.918	pathogenic	0.137	Stabilizing	0.994	D	0.757	deleterious	None	None	None	None	N
E/Y	0.5411	ambiguous	0.5932	pathogenic	0.255	Stabilizing	0.979	D	0.711	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.