TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6752	20479;20480;20481	chr2:178727111;178727110;178727109	chr2:179591838;179591837;179591836
N2AB	6435	19528;19529;19530	chr2:178727111;178727110;178727109	chr2:179591838;179591837;179591836
N2A	5508	16747;16748;16749	chr2:178727111;178727110;178727109	chr2:179591838;179591837;179591836
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-51
• Domain position: 86
• Structural Position: 171
• Q(SASA): 0.2857
• 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
S/I	None	None	0.999	N	0.75	0.515	0.787134533841	gnomAD-4.0.0	1.65984E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.98877E-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
S/A	0.1269	likely_benign	0.1318	benign	-0.579	Destabilizing	0.68	D	0.47	neutral	None	None	None	None	N
S/C	0.3643	ambiguous	0.3147	benign	-0.331	Destabilizing	0.276	N	0.455	neutral	D	0.534275238	None	None	N
S/D	0.8452	likely_pathogenic	0.8647	pathogenic	-0.411	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
S/E	0.8445	likely_pathogenic	0.8732	pathogenic	-0.474	Destabilizing	1.0	D	0.585	neutral	None	None	None	None	N
S/F	0.3338	likely_benign	0.4006	ambiguous	-1.035	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
S/G	0.2175	likely_benign	0.1904	benign	-0.748	Destabilizing	0.995	D	0.533	neutral	N	0.512434773	None	None	N
S/H	0.6117	likely_pathogenic	0.6591	pathogenic	-1.364	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
S/I	0.4069	ambiguous	0.4089	ambiguous	-0.247	Destabilizing	0.999	D	0.75	deleterious	N	0.512941752	None	None	N
S/K	0.914	likely_pathogenic	0.9313	pathogenic	-0.678	Destabilizing	1.0	D	0.562	neutral	None	None	None	None	N
S/L	0.1887	likely_benign	0.2001	benign	-0.247	Destabilizing	0.996	D	0.665	neutral	None	None	None	None	N
S/M	0.3988	ambiguous	0.3678	ambiguous	0.225	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
S/N	0.4005	ambiguous	0.3878	ambiguous	-0.481	Destabilizing	0.993	D	0.585	neutral	N	0.496456885	None	None	N
S/P	0.772	likely_pathogenic	0.7647	pathogenic	-0.327	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
S/Q	0.7548	likely_pathogenic	0.7733	pathogenic	-0.785	Destabilizing	1.0	D	0.612	neutral	None	None	None	None	N
S/R	0.855	likely_pathogenic	0.8842	pathogenic	-0.462	Destabilizing	1.0	D	0.698	prob.neutral	N	0.497760332	None	None	N
S/T	0.1429	likely_benign	0.1427	benign	-0.528	Destabilizing	0.926	D	0.514	neutral	D	0.529421806	None	None	N
S/V	0.3777	ambiguous	0.376	ambiguous	-0.327	Destabilizing	0.997	D	0.7	prob.neutral	None	None	None	None	N
S/W	0.6179	likely_pathogenic	0.6742	pathogenic	-1.005	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
S/Y	0.3697	ambiguous	0.4307	ambiguous	-0.741	Destabilizing	1.0	D	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.