TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25859	77800;77801;77802	chr2:178568557;178568556;178568555	chr2:179433284;179433283;179433282
N2AB	24218	72877;72878;72879	chr2:178568557;178568556;178568555	chr2:179433284;179433283;179433282
N2A	23291	70096;70097;70098	chr2:178568557;178568556;178568555	chr2:179433284;179433283;179433282
N2B	16794	50605;50606;50607	chr2:178568557;178568556;178568555	chr2:179433284;179433283;179433282
Novex-1	16919	50980;50981;50982	chr2:178568557;178568556;178568555	chr2:179433284;179433283;179433282
Novex-2	16986	51181;51182;51183	chr2:178568557;178568556;178568555	chr2:179433284;179433283;179433282
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-136
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.3979
• 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/D	None	None	0.006	N	0.185	0.04	0.166414681773	gnomAD-4.0.0	1.59193E-06	None	None	None	None	N	None	0	0	None	0	2.77485E-05	None	0	0	0	0	0
E/K	rs1706857293	None	0.822	N	0.394	0.169	0.191931220699	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs1706857293	None	0.822	N	0.394	0.169	0.191931220699	gnomAD-4.0.0	6.57765E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47089E-05	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	0.4229	ambiguous	0.4298	ambiguous	-0.564	Destabilizing	0.822	D	0.367	neutral	N	0.491398483	None	None	N
E/C	0.9612	likely_pathogenic	0.963	pathogenic	-0.02	Destabilizing	0.998	D	0.62	neutral	None	None	None	None	N
E/D	0.1174	likely_benign	0.1241	benign	-0.43	Destabilizing	0.006	N	0.185	neutral	N	0.411030758	None	None	N
E/F	0.9424	likely_pathogenic	0.9487	pathogenic	-0.497	Destabilizing	0.993	D	0.546	neutral	None	None	None	None	N
E/G	0.3087	likely_benign	0.3141	benign	-0.789	Destabilizing	0.698	D	0.393	neutral	N	0.490878408	None	None	N
E/H	0.8358	likely_pathogenic	0.8413	pathogenic	-0.511	Destabilizing	0.978	D	0.355	neutral	None	None	None	None	N
E/I	0.8491	likely_pathogenic	0.8546	pathogenic	0.007	Stabilizing	0.978	D	0.548	neutral	None	None	None	None	N
E/K	0.6028	likely_pathogenic	0.5977	pathogenic	0.106	Stabilizing	0.822	D	0.394	neutral	N	0.472060574	None	None	N
E/L	0.8307	likely_pathogenic	0.8395	pathogenic	0.007	Stabilizing	0.978	D	0.483	neutral	None	None	None	None	N
E/M	0.8049	likely_pathogenic	0.8081	pathogenic	0.317	Stabilizing	0.998	D	0.505	neutral	None	None	None	None	N
E/N	0.3762	ambiguous	0.3773	ambiguous	-0.151	Destabilizing	0.019	N	0.3	neutral	None	None	None	None	N
E/P	0.9699	likely_pathogenic	0.9713	pathogenic	-0.163	Destabilizing	0.993	D	0.373	neutral	None	None	None	None	N
E/Q	0.4008	ambiguous	0.3939	ambiguous	-0.115	Destabilizing	0.822	D	0.419	neutral	N	0.499652607	None	None	N
E/R	0.7661	likely_pathogenic	0.7636	pathogenic	0.244	Stabilizing	0.956	D	0.375	neutral	None	None	None	None	N
E/S	0.4523	ambiguous	0.4511	ambiguous	-0.359	Destabilizing	0.754	D	0.345	neutral	None	None	None	None	N
E/T	0.6151	likely_pathogenic	0.6179	pathogenic	-0.178	Destabilizing	0.86	D	0.395	neutral	None	None	None	None	N
E/V	0.6676	likely_pathogenic	0.6707	pathogenic	-0.163	Destabilizing	0.97	D	0.443	neutral	N	0.462542196	None	None	N
E/W	0.9813	likely_pathogenic	0.9827	pathogenic	-0.351	Destabilizing	0.998	D	0.664	neutral	None	None	None	None	N
E/Y	0.8451	likely_pathogenic	0.8606	pathogenic	-0.264	Destabilizing	0.993	D	0.507	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.