TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26550	79873;79874;79875	chr2:178566484;178566483;178566482	chr2:179431211;179431210;179431209
N2AB	24909	74950;74951;74952	chr2:178566484;178566483;178566482	chr2:179431211;179431210;179431209
N2A	23982	72169;72170;72171	chr2:178566484;178566483;178566482	chr2:179431211;179431210;179431209
N2B	17485	52678;52679;52680	chr2:178566484;178566483;178566482	chr2:179431211;179431210;179431209
Novex-1	17610	53053;53054;53055	chr2:178566484;178566483;178566482	chr2:179431211;179431210;179431209
Novex-2	17677	53254;53255;53256	chr2:178566484;178566483;178566482	chr2:179431211;179431210;179431209
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: Fn3-81
• Domain position: 64
• Structural Position: 93
• Q(SASA): 0.1319
• 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/T	None	None	0.822	N	0.76	0.483	0.679538700149	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.815	likely_pathogenic	0.7962	pathogenic	-2.07	Highly Destabilizing	0.754	D	0.735	prob.delet.	None	None	None	None	N
I/C	0.8535	likely_pathogenic	0.8476	pathogenic	-1.703	Destabilizing	0.994	D	0.739	prob.delet.	None	None	None	None	N
I/D	0.9874	likely_pathogenic	0.9856	pathogenic	-1.539	Destabilizing	0.993	D	0.846	deleterious	None	None	None	None	N
I/E	0.9782	likely_pathogenic	0.9742	pathogenic	-1.292	Destabilizing	0.978	D	0.847	deleterious	None	None	None	None	N
I/F	0.2866	likely_benign	0.2922	benign	-1.174	Destabilizing	0.942	D	0.759	deleterious	N	0.479789029	None	None	N
I/G	0.9661	likely_pathogenic	0.9611	pathogenic	-2.618	Highly Destabilizing	0.978	D	0.844	deleterious	None	None	None	None	N
I/H	0.9546	likely_pathogenic	0.9518	pathogenic	-1.97	Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
I/K	0.9421	likely_pathogenic	0.9396	pathogenic	-1.436	Destabilizing	0.978	D	0.847	deleterious	None	None	None	None	N
I/L	0.1569	likely_benign	0.1492	benign	-0.496	Destabilizing	0.294	N	0.442	neutral	N	0.501871767	None	None	N
I/M	0.1644	likely_benign	0.1659	benign	-0.702	Destabilizing	0.942	D	0.725	prob.delet.	N	0.494440698	None	None	N
I/N	0.8986	likely_pathogenic	0.8903	pathogenic	-1.81	Destabilizing	0.99	D	0.845	deleterious	D	0.524408237	None	None	N
I/P	0.9799	likely_pathogenic	0.9789	pathogenic	-1.0	Destabilizing	0.993	D	0.847	deleterious	None	None	None	None	N
I/Q	0.9591	likely_pathogenic	0.9536	pathogenic	-1.558	Destabilizing	0.993	D	0.859	deleterious	None	None	None	None	N
I/R	0.9292	likely_pathogenic	0.924	pathogenic	-1.393	Destabilizing	0.978	D	0.855	deleterious	None	None	None	None	N
I/S	0.9052	likely_pathogenic	0.8942	pathogenic	-2.638	Highly Destabilizing	0.942	D	0.815	deleterious	N	0.501188648	None	None	N
I/T	0.8763	likely_pathogenic	0.8666	pathogenic	-2.212	Highly Destabilizing	0.822	D	0.76	deleterious	N	0.506050493	None	None	N
I/V	0.1133	likely_benign	0.1056	benign	-1.0	Destabilizing	0.006	N	0.177	neutral	N	0.396168454	None	None	N
I/W	0.9386	likely_pathogenic	0.9445	pathogenic	-1.377	Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	N
I/Y	0.7461	likely_pathogenic	0.7635	pathogenic	-1.095	Destabilizing	0.978	D	0.759	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.