TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29458	88597;88598;88599	chr2:178555087;178555086;178555085	chr2:179419814;179419813;179419812
N2AB	27817	83674;83675;83676	chr2:178555087;178555086;178555085	chr2:179419814;179419813;179419812
N2A	26890	80893;80894;80895	chr2:178555087;178555086;178555085	chr2:179419814;179419813;179419812
N2B	20393	61402;61403;61404	chr2:178555087;178555086;178555085	chr2:179419814;179419813;179419812
Novex-1	20518	61777;61778;61779	chr2:178555087;178555086;178555085	chr2:179419814;179419813;179419812
Novex-2	20585	61978;61979;61980	chr2:178555087;178555086;178555085	chr2:179419814;179419813;179419812
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-146
• Domain position: 15
• Structural Position: 28
• Q(SASA): 0.1167
• 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/L	rs1575553466	None	0.898	N	0.535	0.131	0.36256342048	gnomAD-4.0.0	3.60099E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.09898E-04

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	0.6886	likely_pathogenic	0.661	pathogenic	-1.503	Destabilizing	0.977	D	0.545	neutral	N	0.500866115	None	None	N
V/C	0.8758	likely_pathogenic	0.8821	pathogenic	-1.149	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
V/D	0.9894	likely_pathogenic	0.9892	pathogenic	-0.996	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
V/E	0.9748	likely_pathogenic	0.9712	pathogenic	-0.839	Destabilizing	0.999	D	0.816	deleterious	N	0.499492083	None	None	N
V/F	0.4365	ambiguous	0.4136	ambiguous	-0.826	Destabilizing	0.995	D	0.837	deleterious	None	None	None	None	N
V/G	0.8435	likely_pathogenic	0.8334	pathogenic	-1.978	Destabilizing	0.999	D	0.834	deleterious	N	0.487971194	None	None	N
V/H	0.9879	likely_pathogenic	0.9854	pathogenic	-1.443	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/I	0.0848	likely_benign	0.0865	benign	-0.234	Destabilizing	0.15	N	0.273	neutral	None	None	None	None	N
V/K	0.9706	likely_pathogenic	0.9639	pathogenic	-1.095	Destabilizing	0.998	D	0.819	deleterious	None	None	None	None	N
V/L	0.3091	likely_benign	0.308	benign	-0.234	Destabilizing	0.898	D	0.535	neutral	N	0.47850933	None	None	N
V/M	0.3484	ambiguous	0.3336	benign	-0.336	Destabilizing	0.993	D	0.776	deleterious	N	0.499238594	None	None	N
V/N	0.9726	likely_pathogenic	0.9724	pathogenic	-1.241	Destabilizing	0.999	D	0.864	deleterious	None	None	None	None	N
V/P	0.9819	likely_pathogenic	0.9796	pathogenic	-0.624	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
V/Q	0.963	likely_pathogenic	0.957	pathogenic	-1.127	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
V/R	0.9526	likely_pathogenic	0.9427	pathogenic	-0.92	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
V/S	0.9218	likely_pathogenic	0.9186	pathogenic	-1.979	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
V/T	0.8251	likely_pathogenic	0.8191	pathogenic	-1.664	Destabilizing	0.983	D	0.658	neutral	None	None	None	None	N
V/W	0.9812	likely_pathogenic	0.9748	pathogenic	-1.132	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/Y	0.9377	likely_pathogenic	0.9284	pathogenic	-0.749	Destabilizing	0.999	D	0.842	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.