TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27303	82132;82133;82134	chr2:178564225;178564224;178564223	chr2:179428952;179428951;179428950
N2AB	25662	77209;77210;77211	chr2:178564225;178564224;178564223	chr2:179428952;179428951;179428950
N2A	24735	74428;74429;74430	chr2:178564225;178564224;178564223	chr2:179428952;179428951;179428950
N2B	18238	54937;54938;54939	chr2:178564225;178564224;178564223	chr2:179428952;179428951;179428950
Novex-1	18363	55312;55313;55314	chr2:178564225;178564224;178564223	chr2:179428952;179428951;179428950
Novex-2	18430	55513;55514;55515	chr2:178564225;178564224;178564223	chr2:179428952;179428951;179428950
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-140
• Domain position: 26
• Structural Position: 42
• Q(SASA): 0.5759
• 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
P/L	None	None	1.0	D	0.772	0.747	0.75814979803	gnomAD-4.0.0	2.05314E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69841E-06	0	0
P/R	None	None	1.0	D	0.798	0.748	0.604839314244	gnomAD-4.0.0	6.8438E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99471E-07	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
P/A	0.969	likely_pathogenic	0.9665	pathogenic	-0.597	Destabilizing	1.0	D	0.749	deleterious	D	0.559810049	None	None	I
P/C	0.9976	likely_pathogenic	0.9973	pathogenic	-0.635	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
P/D	0.9937	likely_pathogenic	0.993	pathogenic	-0.438	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
P/E	0.9931	likely_pathogenic	0.9921	pathogenic	-0.543	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
P/F	0.9983	likely_pathogenic	0.9979	pathogenic	-0.758	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
P/G	0.9889	likely_pathogenic	0.9885	pathogenic	-0.742	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
P/H	0.991	likely_pathogenic	0.989	pathogenic	-0.285	Destabilizing	1.0	D	0.794	deleterious	D	0.644049318	None	None	I
P/I	0.9862	likely_pathogenic	0.9841	pathogenic	-0.356	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
P/K	0.9942	likely_pathogenic	0.9932	pathogenic	-0.58	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
P/L	0.9657	likely_pathogenic	0.9597	pathogenic	-0.356	Destabilizing	1.0	D	0.772	deleterious	D	0.644049318	None	None	I
P/M	0.9907	likely_pathogenic	0.9895	pathogenic	-0.416	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
P/N	0.9923	likely_pathogenic	0.9919	pathogenic	-0.308	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
P/Q	0.9906	likely_pathogenic	0.9898	pathogenic	-0.546	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
P/R	0.9859	likely_pathogenic	0.9844	pathogenic	-0.034	Destabilizing	1.0	D	0.798	deleterious	D	0.643645709	None	None	I
P/S	0.9921	likely_pathogenic	0.9914	pathogenic	-0.658	Destabilizing	1.0	D	0.753	deleterious	D	0.577407325	None	None	I
P/T	0.974	likely_pathogenic	0.9706	pathogenic	-0.663	Destabilizing	1.0	D	0.75	deleterious	D	0.618107598	None	None	I
P/V	0.9736	likely_pathogenic	0.9708	pathogenic	-0.402	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
P/W	0.9988	likely_pathogenic	0.9985	pathogenic	-0.845	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
P/Y	0.9961	likely_pathogenic	0.9953	pathogenic	-0.561	Destabilizing	1.0	D	0.826	deleterious	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.