TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33686	101281;101282;101283	chr2:178535559;178535558;178535557	chr2:179400286;179400285;179400284
N2AB	32045	96358;96359;96360	chr2:178535559;178535558;178535557	chr2:179400286;179400285;179400284
N2A	31118	93577;93578;93579	chr2:178535559;178535558;178535557	chr2:179400286;179400285;179400284
N2B	24621	74086;74087;74088	chr2:178535559;178535558;178535557	chr2:179400286;179400285;179400284
Novex-1	24746	74461;74462;74463	chr2:178535559;178535558;178535557	chr2:179400286;179400285;179400284
Novex-2	24813	74662;74663;74664	chr2:178535559;178535558;178535557	chr2:179400286;179400285;179400284
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-159
• Domain position: 91
• Structural Position: 177
• Q(SASA): 0.166
• 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
V/M	rs1194467385	None	1.0	D	0.859	0.672	0.713529394019	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	6.54E-05	0	0	0	None	0	0	0	0	0
V/M	rs1194467385	None	1.0	D	0.859	0.672	0.713529394019	gnomAD-4.0.0	1.31385E-05	None	None	None	None	N	None	2.41196E-05	6.54365E-05	None	0	0	None	0	0	0	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
V/A	0.9155	likely_pathogenic	0.8538	pathogenic	-1.792	Destabilizing	1.0	D	0.793	deleterious	D	0.596462693	None	None	N
V/C	0.9882	likely_pathogenic	0.9799	pathogenic	-1.484	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/D	0.9989	likely_pathogenic	0.9966	pathogenic	-2.281	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/E	0.9966	likely_pathogenic	0.9906	pathogenic	-2.265	Highly Destabilizing	1.0	D	0.845	deleterious	D	0.597068106	None	None	N
V/F	0.982	likely_pathogenic	0.9362	pathogenic	-1.483	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
V/G	0.9785	likely_pathogenic	0.9559	pathogenic	-2.119	Highly Destabilizing	1.0	D	0.845	deleterious	D	0.597068106	None	None	N
V/H	0.9995	likely_pathogenic	0.9984	pathogenic	-1.603	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/I	0.2048	likely_benign	0.1429	benign	-0.969	Destabilizing	0.994	D	0.697	prob.neutral	None	None	None	None	N
V/K	0.9982	likely_pathogenic	0.9943	pathogenic	-1.449	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/L	0.9545	likely_pathogenic	0.8883	pathogenic	-0.969	Destabilizing	0.993	D	0.776	deleterious	D	0.578193125	None	None	N
V/M	0.9387	likely_pathogenic	0.8377	pathogenic	-0.841	Destabilizing	1.0	D	0.859	deleterious	D	0.596664498	None	None	N
V/N	0.9965	likely_pathogenic	0.9906	pathogenic	-1.391	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
V/P	0.9952	likely_pathogenic	0.9921	pathogenic	-1.212	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
V/Q	0.9979	likely_pathogenic	0.9939	pathogenic	-1.603	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
V/R	0.9962	likely_pathogenic	0.9889	pathogenic	-0.909	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/S	0.9796	likely_pathogenic	0.9561	pathogenic	-1.876	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
V/T	0.8821	likely_pathogenic	0.8262	pathogenic	-1.757	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
V/W	0.9998	likely_pathogenic	0.9992	pathogenic	-1.688	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/Y	0.9989	likely_pathogenic	0.9953	pathogenic	-1.394	Destabilizing	1.0	D	0.851	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.