TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31911	95956;95957;95958	chr2:178544498;178544497;178544496	chr2:179409225;179409224;179409223
N2AB	30270	91033;91034;91035	chr2:178544498;178544497;178544496	chr2:179409225;179409224;179409223
N2A	29343	88252;88253;88254	chr2:178544498;178544497;178544496	chr2:179409225;179409224;179409223
N2B	22846	68761;68762;68763	chr2:178544498;178544497;178544496	chr2:179409225;179409224;179409223
Novex-1	22971	69136;69137;69138	chr2:178544498;178544497;178544496	chr2:179409225;179409224;179409223
Novex-2	23038	69337;69338;69339	chr2:178544498;178544497;178544496	chr2:179409225;179409224;179409223
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-121
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.2296
• 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/E	rs778837156	None	0.993	N	0.723	0.304	None	gnomAD-4.0.0	1.64654E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.98755E-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	0.1597	likely_benign	0.1151	benign	-0.861	Destabilizing	0.053	N	0.318	neutral	N	0.470835352	None	None	N
G/C	0.3258	likely_benign	0.2489	benign	-1.166	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
G/D	0.7386	likely_pathogenic	0.6082	pathogenic	-1.561	Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
G/E	0.6885	likely_pathogenic	0.5724	pathogenic	-1.603	Destabilizing	0.993	D	0.723	prob.delet.	N	0.479785348	None	None	N
G/F	0.7806	likely_pathogenic	0.7059	pathogenic	-1.167	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
G/H	0.8133	likely_pathogenic	0.7207	pathogenic	-1.414	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
G/I	0.6139	likely_pathogenic	0.5058	ambiguous	-0.468	Destabilizing	0.995	D	0.8	deleterious	None	None	None	None	N
G/K	0.8899	likely_pathogenic	0.8361	pathogenic	-1.272	Destabilizing	0.995	D	0.726	prob.delet.	None	None	None	None	N
G/L	0.5795	likely_pathogenic	0.4767	ambiguous	-0.468	Destabilizing	0.995	D	0.713	prob.delet.	None	None	None	None	N
G/M	0.6529	likely_pathogenic	0.5609	ambiguous	-0.483	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
G/N	0.6774	likely_pathogenic	0.601	pathogenic	-1.048	Destabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	N
G/P	0.9597	likely_pathogenic	0.954	pathogenic	-0.56	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
G/Q	0.736	likely_pathogenic	0.6393	pathogenic	-1.247	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
G/R	0.8068	likely_pathogenic	0.718	pathogenic	-0.987	Destabilizing	0.997	D	0.772	deleterious	N	0.479913933	None	None	N
G/S	0.131	likely_benign	0.1083	benign	-1.3	Destabilizing	0.966	D	0.501	neutral	None	None	None	None	N
G/T	0.3706	ambiguous	0.2914	benign	-1.269	Destabilizing	0.995	D	0.668	neutral	None	None	None	None	N
G/V	0.4729	ambiguous	0.3639	ambiguous	-0.56	Destabilizing	0.987	D	0.702	prob.neutral	N	0.508564799	None	None	N
G/W	0.784	likely_pathogenic	0.7036	pathogenic	-1.51	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
G/Y	0.7241	likely_pathogenic	0.6231	pathogenic	-1.1	Destabilizing	1.0	D	0.79	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.