TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1742	5449;5450;5451	chr2:178776640;178776639;178776638	chr2:179641367;179641366;179641365
N2AB	1742	5449;5450;5451	chr2:178776640;178776639;178776638	chr2:179641367;179641366;179641365
N2A	1742	5449;5450;5451	chr2:178776640;178776639;178776638	chr2:179641367;179641366;179641365
N2B	1696	5311;5312;5313	chr2:178776640;178776639;178776638	chr2:179641367;179641366;179641365
Novex-1	1696	5311;5312;5313	chr2:178776640;178776639;178776638	chr2:179641367;179641366;179641365
Novex-2	1696	5311;5312;5313	chr2:178776640;178776639;178776638	chr2:179641367;179641366;179641365
Novex-3	1742	5449;5450;5451	chr2:178776640;178776639;178776638	chr2:179641367;179641366;179641365

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-8
• Domain position: 40
• Structural Position: 52
• Q(SASA): 0.366
• 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
G/A	None	None	0.992	D	0.464	0.813	0.526437037968	gnomAD-4.0.0	1.59067E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85651E-06	0	0
G/R	None	None	0.999	D	0.717	0.686	0.826022559999	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
G/A	0.6625	likely_pathogenic	0.6788	pathogenic	-0.371	Destabilizing	0.992	D	0.464	neutral	D	0.726284166	None	None	N
G/C	0.8772	likely_pathogenic	0.8698	pathogenic	-0.826	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
G/D	0.6483	likely_pathogenic	0.6613	pathogenic	-0.836	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
G/E	0.7232	likely_pathogenic	0.7402	pathogenic	-0.998	Destabilizing	0.999	D	0.703	prob.neutral	D	0.705153973	None	None	N
G/F	0.9866	likely_pathogenic	0.9882	pathogenic	-1.053	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
G/H	0.8613	likely_pathogenic	0.869	pathogenic	-0.684	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
G/I	0.9744	likely_pathogenic	0.9768	pathogenic	-0.455	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
G/K	0.8764	likely_pathogenic	0.8796	pathogenic	-1.025	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
G/L	0.9546	likely_pathogenic	0.9583	pathogenic	-0.455	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
G/M	0.9542	likely_pathogenic	0.9578	pathogenic	-0.436	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
G/N	0.4785	ambiguous	0.4845	ambiguous	-0.582	Destabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	N
G/P	0.9989	likely_pathogenic	0.9992	pathogenic	-0.392	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
G/Q	0.6994	likely_pathogenic	0.7177	pathogenic	-0.893	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
G/R	0.7939	likely_pathogenic	0.8036	pathogenic	-0.524	Destabilizing	0.999	D	0.717	prob.delet.	D	0.709168081	None	None	N
G/S	0.235	likely_benign	0.2457	benign	-0.701	Destabilizing	0.927	D	0.401	neutral	None	None	None	None	N
G/T	0.7701	likely_pathogenic	0.7882	pathogenic	-0.801	Destabilizing	0.998	D	0.716	prob.delet.	None	None	None	None	N
G/V	0.95	likely_pathogenic	0.9545	pathogenic	-0.392	Destabilizing	0.999	D	0.715	prob.delet.	D	0.796931912	None	None	N
G/W	0.979	likely_pathogenic	0.9815	pathogenic	-1.226	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
G/Y	0.9646	likely_pathogenic	0.9676	pathogenic	-0.887	Destabilizing	1.0	D	0.74	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.