TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32377	97354;97355;97356	chr2:178542725;178542724;178542723	chr2:179407452;179407451;179407450
N2AB	30736	92431;92432;92433	chr2:178542725;178542724;178542723	chr2:179407452;179407451;179407450
N2A	29809	89650;89651;89652	chr2:178542725;178542724;178542723	chr2:179407452;179407451;179407450
N2B	23312	70159;70160;70161	chr2:178542725;178542724;178542723	chr2:179407452;179407451;179407450
Novex-1	23437	70534;70535;70536	chr2:178542725;178542724;178542723	chr2:179407452;179407451;179407450
Novex-2	23504	70735;70736;70737	chr2:178542725;178542724;178542723	chr2:179407452;179407451;179407450
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-154
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1093
• 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
Y/C	None	None	0.997	D	0.823	0.843	0.746720708991	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
Y/H	rs1695198854	None	0.032	D	0.523	0.723	0.441844919209	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
Y/A	0.9979	likely_pathogenic	0.997	pathogenic	-1.466	Destabilizing	0.86	D	0.805	deleterious	None	None	None	None	N
Y/C	0.9822	likely_pathogenic	0.971	pathogenic	-0.969	Destabilizing	0.997	D	0.823	deleterious	D	0.598400373	None	None	N
Y/D	0.9987	likely_pathogenic	0.9978	pathogenic	-2.365	Highly Destabilizing	0.942	D	0.863	deleterious	D	0.614651899	None	None	N
Y/E	0.9994	likely_pathogenic	0.9992	pathogenic	-2.122	Highly Destabilizing	0.956	D	0.824	deleterious	None	None	None	None	N
Y/F	0.3222	likely_benign	0.301	benign	-0.312	Destabilizing	0.904	D	0.693	prob.neutral	D	0.570642415	None	None	N
Y/G	0.9943	likely_pathogenic	0.993	pathogenic	-1.896	Destabilizing	0.956	D	0.847	deleterious	None	None	None	None	N
Y/H	0.9919	likely_pathogenic	0.9859	pathogenic	-1.629	Destabilizing	0.032	N	0.523	neutral	D	0.614450095	None	None	N
Y/I	0.9535	likely_pathogenic	0.9491	pathogenic	-0.061	Destabilizing	0.978	D	0.801	deleterious	None	None	None	None	N
Y/K	0.9992	likely_pathogenic	0.9989	pathogenic	-1.387	Destabilizing	0.956	D	0.841	deleterious	None	None	None	None	N
Y/L	0.9217	likely_pathogenic	0.922	pathogenic	-0.061	Destabilizing	0.86	D	0.78	deleterious	None	None	None	None	N
Y/M	0.9778	likely_pathogenic	0.9718	pathogenic	-0.213	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
Y/N	0.9917	likely_pathogenic	0.9878	pathogenic	-2.326	Highly Destabilizing	0.89	D	0.843	deleterious	D	0.614651899	None	None	N
Y/P	0.9996	likely_pathogenic	0.9995	pathogenic	-0.541	Destabilizing	0.993	D	0.858	deleterious	None	None	None	None	N
Y/Q	0.9994	likely_pathogenic	0.9991	pathogenic	-1.795	Destabilizing	0.956	D	0.792	deleterious	None	None	None	None	N
Y/R	0.9981	likely_pathogenic	0.9974	pathogenic	-1.935	Destabilizing	0.956	D	0.841	deleterious	None	None	None	None	N
Y/S	0.9973	likely_pathogenic	0.9962	pathogenic	-2.539	Highly Destabilizing	0.942	D	0.824	deleterious	D	0.614651899	None	None	N
Y/T	0.9981	likely_pathogenic	0.9975	pathogenic	-2.147	Highly Destabilizing	0.978	D	0.841	deleterious	None	None	None	None	N
Y/V	0.943	likely_pathogenic	0.9393	pathogenic	-0.541	Destabilizing	0.978	D	0.803	deleterious	None	None	None	None	N
Y/W	0.9211	likely_pathogenic	0.8919	pathogenic	0.157	Stabilizing	0.998	D	0.721	prob.delet.	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.