TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26035	78328;78329;78330	chr2:178568029;178568028;178568027	chr2:179432756;179432755;179432754
N2AB	24394	73405;73406;73407	chr2:178568029;178568028;178568027	chr2:179432756;179432755;179432754
N2A	23467	70624;70625;70626	chr2:178568029;178568028;178568027	chr2:179432756;179432755;179432754
N2B	16970	51133;51134;51135	chr2:178568029;178568028;178568027	chr2:179432756;179432755;179432754
Novex-1	17095	51508;51509;51510	chr2:178568029;178568028;178568027	chr2:179432756;179432755;179432754
Novex-2	17162	51709;51710;51711	chr2:178568029;178568028;178568027	chr2:179432756;179432755;179432754
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: Fn3-77
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.7979
• 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
I/V	None	None	0.011	N	0.387	0.151	0.446010312102	gnomAD-4.0.0	1.59217E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85964E-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
I/A	0.9392	likely_pathogenic	0.9484	pathogenic	-0.495	Destabilizing	0.845	D	0.525	neutral	None	None	None	None	I
I/C	0.9835	likely_pathogenic	0.9848	pathogenic	-0.798	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	I
I/D	0.9941	likely_pathogenic	0.9939	pathogenic	-0.159	Destabilizing	0.996	D	0.655	neutral	None	None	None	None	I
I/E	0.9923	likely_pathogenic	0.992	pathogenic	-0.238	Destabilizing	0.987	D	0.652	neutral	None	None	None	None	I
I/F	0.6825	likely_pathogenic	0.7158	pathogenic	-0.607	Destabilizing	0.967	D	0.506	neutral	N	0.493080664	None	None	I
I/G	0.9889	likely_pathogenic	0.9912	pathogenic	-0.601	Destabilizing	0.987	D	0.658	neutral	None	None	None	None	I
I/H	0.9805	likely_pathogenic	0.9805	pathogenic	0.115	Stabilizing	0.999	D	0.661	neutral	None	None	None	None	I
I/K	0.9757	likely_pathogenic	0.9745	pathogenic	-0.32	Destabilizing	0.987	D	0.653	neutral	None	None	None	None	I
I/L	0.2015	likely_benign	0.2587	benign	-0.329	Destabilizing	0.426	N	0.491	neutral	N	0.472765155	None	None	I
I/M	0.4192	ambiguous	0.4647	ambiguous	-0.645	Destabilizing	0.983	D	0.505	neutral	N	0.477343039	None	None	I
I/N	0.9454	likely_pathogenic	0.9478	pathogenic	-0.218	Destabilizing	0.994	D	0.654	neutral	N	0.487097102	None	None	I
I/P	0.9702	likely_pathogenic	0.973	pathogenic	-0.358	Destabilizing	0.996	D	0.664	neutral	None	None	None	None	I
I/Q	0.9816	likely_pathogenic	0.9815	pathogenic	-0.371	Destabilizing	0.996	D	0.647	neutral	None	None	None	None	I
I/R	0.9577	likely_pathogenic	0.953	pathogenic	0.131	Stabilizing	0.987	D	0.65	neutral	None	None	None	None	I
I/S	0.9428	likely_pathogenic	0.9477	pathogenic	-0.621	Destabilizing	0.983	D	0.583	neutral	N	0.466145827	None	None	I
I/T	0.9516	likely_pathogenic	0.9582	pathogenic	-0.599	Destabilizing	0.892	D	0.501	neutral	N	0.470994286	None	None	I
I/V	0.2568	likely_benign	0.2887	benign	-0.358	Destabilizing	0.011	N	0.387	neutral	N	0.500239758	None	None	I
I/W	0.9804	likely_pathogenic	0.9806	pathogenic	-0.62	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	I
I/Y	0.9336	likely_pathogenic	0.933	pathogenic	-0.395	Destabilizing	0.987	D	0.532	neutral	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.