TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33404	100435;100436;100437	chr2:178536537;178536536;178536535	chr2:179401264;179401263;179401262
N2AB	31763	95512;95513;95514	chr2:178536537;178536536;178536535	chr2:179401264;179401263;179401262
N2A	30836	92731;92732;92733	chr2:178536537;178536536;178536535	chr2:179401264;179401263;179401262
N2B	24339	73240;73241;73242	chr2:178536537;178536536;178536535	chr2:179401264;179401263;179401262
Novex-1	24464	73615;73616;73617	chr2:178536537;178536536;178536535	chr2:179401264;179401263;179401262
Novex-2	24531	73816;73817;73818	chr2:178536537;178536536;178536535	chr2:179401264;179401263;179401262
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-131
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.3198
• 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/I	None	None	None	N	0.119	0.144	0.0884992946249	gnomAD-4.0.0	2.92403E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.73653E-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
V/A	0.2503	likely_benign	0.2245	benign	-1.296	Destabilizing	None	N	0.132	neutral	N	0.492297852	None	None	N
V/C	0.7762	likely_pathogenic	0.702	pathogenic	-1.169	Destabilizing	0.628	D	0.467	neutral	None	None	None	None	N
V/D	0.6839	likely_pathogenic	0.7296	pathogenic	-0.949	Destabilizing	0.055	N	0.593	neutral	N	0.493617777	None	None	N
V/E	0.526	ambiguous	0.5368	ambiguous	-0.989	Destabilizing	0.072	N	0.544	neutral	None	None	None	None	N
V/F	0.2795	likely_benign	0.2679	benign	-1.245	Destabilizing	0.029	N	0.539	neutral	N	0.476945554	None	None	N
V/G	0.3899	ambiguous	0.4084	ambiguous	-1.555	Destabilizing	0.055	N	0.499	neutral	N	0.49002338	None	None	N
V/H	0.779	likely_pathogenic	0.7439	pathogenic	-1.11	Destabilizing	0.864	D	0.53	neutral	None	None	None	None	N
V/I	0.079	likely_benign	0.0706	benign	-0.707	Destabilizing	None	N	0.119	neutral	N	0.420914969	None	None	N
V/K	0.5179	ambiguous	0.5403	ambiguous	-0.99	Destabilizing	0.072	N	0.52	neutral	None	None	None	None	N
V/L	0.2422	likely_benign	0.1983	benign	-0.707	Destabilizing	None	N	0.125	neutral	N	0.506957873	None	None	N
V/M	0.1951	likely_benign	0.1571	benign	-0.588	Destabilizing	0.12	N	0.461	neutral	None	None	None	None	N
V/N	0.4919	ambiguous	0.4549	ambiguous	-0.79	Destabilizing	0.214	N	0.582	neutral	None	None	None	None	N
V/P	0.8063	likely_pathogenic	0.867	pathogenic	-0.868	Destabilizing	0.356	N	0.567	neutral	None	None	None	None	N
V/Q	0.4974	ambiguous	0.4782	ambiguous	-1.013	Destabilizing	0.356	N	0.543	neutral	None	None	None	None	N
V/R	0.4672	ambiguous	0.5087	ambiguous	-0.49	Destabilizing	0.356	N	0.583	neutral	None	None	None	None	N
V/S	0.3456	ambiguous	0.3058	benign	-1.332	Destabilizing	0.003	N	0.392	neutral	None	None	None	None	N
V/T	0.2555	likely_benign	0.2148	benign	-1.258	Destabilizing	0.016	N	0.389	neutral	None	None	None	None	N
V/W	0.9147	likely_pathogenic	0.8991	pathogenic	-1.342	Destabilizing	0.864	D	0.565	neutral	None	None	None	None	N
V/Y	0.733	likely_pathogenic	0.6951	pathogenic	-1.037	Destabilizing	0.356	N	0.536	neutral	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.