TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19828	59707;59708;59709	chr2:178592523;178592522;178592521	chr2:179457250;179457249;179457248
N2AB	18187	54784;54785;54786	chr2:178592523;178592522;178592521	chr2:179457250;179457249;179457248
N2A	17260	52003;52004;52005	chr2:178592523;178592522;178592521	chr2:179457250;179457249;179457248
N2B	10763	32512;32513;32514	chr2:178592523;178592522;178592521	chr2:179457250;179457249;179457248
Novex-1	10888	32887;32888;32889	chr2:178592523;178592522;178592521	chr2:179457250;179457249;179457248
Novex-2	10955	33088;33089;33090	chr2:178592523;178592522;178592521	chr2:179457250;179457249;179457248
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-119
• Domain position: 39
• Structural Position: 59
• Q(SASA): 0.5187
• 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
P/S	None	None	0.362	N	0.308	0.24	None	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
P/A	0.1222	likely_benign	0.1295	benign	-1.487	Destabilizing	0.955	D	0.475	neutral	N	0.482677362	None	None	N
P/C	0.6308	likely_pathogenic	0.6424	pathogenic	-1.017	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
P/D	0.4452	ambiguous	0.5013	ambiguous	-1.173	Destabilizing	0.995	D	0.662	neutral	None	None	None	None	N
P/E	0.4111	ambiguous	0.462	ambiguous	-1.154	Destabilizing	0.995	D	0.65	neutral	None	None	None	None	N
P/F	0.6679	likely_pathogenic	0.6987	pathogenic	-1.128	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
P/G	0.2978	likely_benign	0.3082	benign	-1.823	Destabilizing	0.966	D	0.586	neutral	None	None	None	None	N
P/H	0.3295	likely_benign	0.3423	ambiguous	-1.322	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
P/I	0.4334	ambiguous	0.4842	ambiguous	-0.655	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
P/K	0.4833	ambiguous	0.5352	ambiguous	-1.284	Destabilizing	0.995	D	0.653	neutral	None	None	None	None	N
P/L	0.2228	likely_benign	0.2383	benign	-0.655	Destabilizing	0.993	D	0.725	prob.delet.	N	0.486515704	None	None	N
P/M	0.4358	ambiguous	0.4643	ambiguous	-0.544	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
P/N	0.3714	ambiguous	0.3866	ambiguous	-1.063	Destabilizing	0.995	D	0.734	prob.delet.	None	None	None	None	N
P/Q	0.2937	likely_benign	0.3222	benign	-1.172	Destabilizing	0.997	D	0.727	prob.delet.	D	0.524359916	None	None	N
P/R	0.3994	ambiguous	0.4638	ambiguous	-0.818	Destabilizing	0.993	D	0.74	deleterious	D	0.528053582	None	None	N
P/S	0.1532	likely_benign	0.1553	benign	-1.599	Destabilizing	0.362	N	0.308	neutral	N	0.493402291	None	None	N
P/T	0.1385	likely_benign	0.1494	benign	-1.454	Destabilizing	0.955	D	0.587	neutral	N	0.511161332	None	None	N
P/V	0.2938	likely_benign	0.3346	benign	-0.898	Destabilizing	0.995	D	0.733	prob.delet.	None	None	None	None	N
P/W	0.7948	likely_pathogenic	0.827	pathogenic	-1.31	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
P/Y	0.6077	likely_pathogenic	0.6451	pathogenic	-1.026	Destabilizing	1.0	D	0.749	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.