TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17027	51304;51305;51306	chr2:178611050;178611049;178611048	chr2:179475777;179475776;179475775
N2AB	15386	46381;46382;46383	chr2:178611050;178611049;178611048	chr2:179475777;179475776;179475775
N2A	14459	43600;43601;43602	chr2:178611050;178611049;178611048	chr2:179475777;179475776;179475775
N2B	7962	24109;24110;24111	chr2:178611050;178611049;178611048	chr2:179475777;179475776;179475775
Novex-1	8087	24484;24485;24486	chr2:178611050;178611049;178611048	chr2:179475777;179475776;179475775
Novex-2	8154	24685;24686;24687	chr2:178611050;178611049;178611048	chr2:179475777;179475776;179475775
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-111
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.0654
• 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
I/F	rs770809063	-1.786	0.001	N	0.423	0.217	0.197625483188	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.35E-05	0
I/F	rs770809063	-1.786	0.001	N	0.423	0.217	0.197625483188	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.42E-05	0	0
I/F	rs770809063	-1.786	0.001	N	0.423	0.217	0.197625483188	gnomAD-4.0.0	6.41386E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.19832E-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
I/A	0.7966	likely_pathogenic	0.8162	pathogenic	-2.69	Highly Destabilizing	0.035	N	0.725	prob.delet.	None	None	None	None	N
I/C	0.8932	likely_pathogenic	0.9139	pathogenic	-2.291	Highly Destabilizing	0.824	D	0.789	deleterious	None	None	None	None	N
I/D	0.998	likely_pathogenic	0.9985	pathogenic	-3.085	Highly Destabilizing	0.555	D	0.857	deleterious	None	None	None	None	N
I/E	0.9937	likely_pathogenic	0.9946	pathogenic	-2.814	Highly Destabilizing	0.555	D	0.842	deleterious	None	None	None	None	N
I/F	0.5164	ambiguous	0.5807	pathogenic	-1.669	Destabilizing	0.001	N	0.423	neutral	N	0.503652305	None	None	N
I/G	0.977	likely_pathogenic	0.9807	pathogenic	-3.29	Highly Destabilizing	0.555	D	0.836	deleterious	None	None	None	None	N
I/H	0.9914	likely_pathogenic	0.9929	pathogenic	-2.854	Highly Destabilizing	0.935	D	0.855	deleterious	None	None	None	None	N
I/K	0.9879	likely_pathogenic	0.9887	pathogenic	-2.015	Highly Destabilizing	0.555	D	0.845	deleterious	None	None	None	None	N
I/L	0.1343	likely_benign	0.1464	benign	-0.926	Destabilizing	None	N	0.386	neutral	N	0.446783279	None	None	N
I/M	0.1748	likely_benign	0.1915	benign	-1.079	Destabilizing	0.317	N	0.642	neutral	N	0.489541094	None	None	N
I/N	0.9725	likely_pathogenic	0.9777	pathogenic	-2.519	Highly Destabilizing	0.741	D	0.859	deleterious	D	0.573764265	None	None	N
I/P	0.9937	likely_pathogenic	0.9955	pathogenic	-1.498	Destabilizing	0.791	D	0.854	deleterious	None	None	None	None	N
I/Q	0.9866	likely_pathogenic	0.9889	pathogenic	-2.287	Highly Destabilizing	0.791	D	0.864	deleterious	None	None	None	None	N
I/R	0.982	likely_pathogenic	0.9832	pathogenic	-1.885	Destabilizing	0.555	D	0.859	deleterious	None	None	None	None	N
I/S	0.9491	likely_pathogenic	0.9575	pathogenic	-3.252	Highly Destabilizing	0.317	N	0.812	deleterious	D	0.57285347	None	None	N
I/T	0.8756	likely_pathogenic	0.9036	pathogenic	-2.814	Highly Destabilizing	0.062	N	0.749	deleterious	D	0.571375218	None	None	N
I/V	0.0751	likely_benign	0.078	benign	-1.498	Destabilizing	None	N	0.307	neutral	N	0.410559698	None	None	N
I/W	0.9902	likely_pathogenic	0.993	pathogenic	-2.064	Highly Destabilizing	0.824	D	0.859	deleterious	None	None	None	None	N
I/Y	0.9521	likely_pathogenic	0.9603	pathogenic	-1.801	Destabilizing	0.235	N	0.764	deleterious	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.