TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35343	106252;106253;106254	chr2:178530588;178530587;178530586	chr2:179395315;179395314;179395313
N2AB	33702	101329;101330;101331	chr2:178530588;178530587;178530586	chr2:179395315;179395314;179395313
N2A	32775	98548;98549;98550	chr2:178530588;178530587;178530586	chr2:179395315;179395314;179395313
N2B	26278	79057;79058;79059	chr2:178530588;178530587;178530586	chr2:179395315;179395314;179395313
Novex-1	26403	79432;79433;79434	chr2:178530588;178530587;178530586	chr2:179395315;179395314;179395313
Novex-2	26470	79633;79634;79635	chr2:178530588;178530587;178530586	chr2:179395315;179395314;179395313
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: Ig-165
• Domain position: 58
• Structural Position: 137
• Q(SASA): 0.2731
• 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/K	rs774519928	-1.431	0.92	N	0.551	0.282	0.277317399466	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
E/K	rs774519928	-1.431	0.92	N	0.551	0.282	0.277317399466	gnomAD-4.0.0	4.77262E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57241E-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	0.3106	likely_benign	0.2673	benign	-1.285	Destabilizing	0.704	D	0.443	neutral	N	0.497002743	None	None	N
E/C	0.9129	likely_pathogenic	0.9018	pathogenic	-1.008	Destabilizing	0.1	N	0.557	neutral	None	None	None	None	N
E/D	0.4864	ambiguous	0.4231	ambiguous	-1.683	Destabilizing	0.704	D	0.493	neutral	N	0.496445383	None	None	N
E/F	0.8794	likely_pathogenic	0.8416	pathogenic	-1.113	Destabilizing	0.997	D	0.638	neutral	None	None	None	None	N
E/G	0.4989	ambiguous	0.3984	ambiguous	-1.681	Destabilizing	0.826	D	0.55	neutral	N	0.513857708	None	None	N
E/H	0.694	likely_pathogenic	0.6335	pathogenic	-1.413	Destabilizing	0.991	D	0.527	neutral	None	None	None	None	N
E/I	0.4738	ambiguous	0.4339	ambiguous	-0.173	Destabilizing	0.982	D	0.634	neutral	None	None	None	None	N
E/K	0.3588	ambiguous	0.2819	benign	-1.708	Destabilizing	0.92	D	0.551	neutral	N	0.47287509	None	None	N
E/L	0.6727	likely_pathogenic	0.6062	pathogenic	-0.173	Destabilizing	0.939	D	0.585	neutral	None	None	None	None	N
E/M	0.614	likely_pathogenic	0.5614	ambiguous	0.489	Stabilizing	0.997	D	0.626	neutral	None	None	None	None	N
E/N	0.5993	likely_pathogenic	0.5401	ambiguous	-1.943	Destabilizing	0.17	N	0.265	neutral	None	None	None	None	N
E/P	0.9962	likely_pathogenic	0.9924	pathogenic	-0.525	Destabilizing	0.997	D	0.565	neutral	None	None	None	None	N
E/Q	0.2016	likely_benign	0.1804	benign	-1.653	Destabilizing	0.959	D	0.512	neutral	N	0.478147624	None	None	N
E/R	0.5354	ambiguous	0.4385	ambiguous	-1.58	Destabilizing	0.969	D	0.513	neutral	None	None	None	None	N
E/S	0.3657	ambiguous	0.3198	benign	-2.516	Highly Destabilizing	0.373	N	0.234	neutral	None	None	None	None	N
E/T	0.3337	likely_benign	0.3034	benign	-2.162	Highly Destabilizing	0.17	N	0.301	neutral	None	None	None	None	N
E/V	0.3227	likely_benign	0.2946	benign	-0.525	Destabilizing	0.92	D	0.581	neutral	N	0.496445383	None	None	N
E/W	0.9728	likely_pathogenic	0.9592	pathogenic	-1.243	Destabilizing	0.999	D	0.682	prob.neutral	None	None	None	None	N
E/Y	0.8473	likely_pathogenic	0.794	pathogenic	-0.994	Destabilizing	0.997	D	0.621	neutral	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.