TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20972	63139;63140;63141	chr2:178588811;178588810;178588809	chr2:179453538;179453537;179453536
N2AB	19331	58216;58217;58218	chr2:178588811;178588810;178588809	chr2:179453538;179453537;179453536
N2A	18404	55435;55436;55437	chr2:178588811;178588810;178588809	chr2:179453538;179453537;179453536
N2B	11907	35944;35945;35946	chr2:178588811;178588810;178588809	chr2:179453538;179453537;179453536
Novex-1	12032	36319;36320;36321	chr2:178588811;178588810;178588809	chr2:179453538;179453537;179453536
Novex-2	12099	36520;36521;36522	chr2:178588811;178588810;178588809	chr2:179453538;179453537;179453536
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: Fn3-40
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3944
• Predicted PPI site: I

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/F	None	None	0.942	N	0.785	0.367	0.543209242439	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.7507	likely_pathogenic	0.6417	pathogenic	-1.882	Destabilizing	0.822	D	0.557	neutral	N	0.506995159	None	None	I
V/C	0.9452	likely_pathogenic	0.9244	pathogenic	-1.45	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	I
V/D	0.9899	likely_pathogenic	0.9808	pathogenic	-2.105	Highly Destabilizing	0.99	D	0.822	deleterious	D	0.522180829	None	None	I
V/E	0.9757	likely_pathogenic	0.9594	pathogenic	-1.968	Destabilizing	0.993	D	0.799	deleterious	None	None	None	None	I
V/F	0.857	likely_pathogenic	0.787	pathogenic	-1.188	Destabilizing	0.942	D	0.785	deleterious	N	0.473752322	None	None	I
V/G	0.8939	likely_pathogenic	0.8207	pathogenic	-2.36	Highly Destabilizing	0.971	D	0.8	deleterious	N	0.481998437	None	None	I
V/H	0.9953	likely_pathogenic	0.9909	pathogenic	-2.096	Highly Destabilizing	0.998	D	0.82	deleterious	None	None	None	None	I
V/I	0.0815	likely_benign	0.0794	benign	-0.597	Destabilizing	0.014	N	0.281	neutral	N	0.444621335	None	None	I
V/K	0.9878	likely_pathogenic	0.9774	pathogenic	-1.597	Destabilizing	0.978	D	0.799	deleterious	None	None	None	None	I
V/L	0.7585	likely_pathogenic	0.6676	pathogenic	-0.597	Destabilizing	0.247	N	0.496	neutral	N	0.521023249	None	None	I
V/M	0.696	likely_pathogenic	0.5873	pathogenic	-0.574	Destabilizing	0.956	D	0.745	deleterious	None	None	None	None	I
V/N	0.9687	likely_pathogenic	0.9413	pathogenic	-1.642	Destabilizing	0.993	D	0.835	deleterious	None	None	None	None	I
V/P	0.8505	likely_pathogenic	0.8152	pathogenic	-0.994	Destabilizing	0.993	D	0.81	deleterious	None	None	None	None	I
V/Q	0.9856	likely_pathogenic	0.9743	pathogenic	-1.607	Destabilizing	0.993	D	0.829	deleterious	None	None	None	None	I
V/R	0.9818	likely_pathogenic	0.9666	pathogenic	-1.332	Destabilizing	0.993	D	0.837	deleterious	None	None	None	None	I
V/S	0.9365	likely_pathogenic	0.8795	pathogenic	-2.26	Highly Destabilizing	0.978	D	0.774	deleterious	None	None	None	None	I
V/T	0.8592	likely_pathogenic	0.7779	pathogenic	-1.987	Destabilizing	0.86	D	0.685	prob.neutral	None	None	None	None	I
V/W	0.9953	likely_pathogenic	0.9922	pathogenic	-1.596	Destabilizing	0.998	D	0.776	deleterious	None	None	None	None	I
V/Y	0.9795	likely_pathogenic	0.9646	pathogenic	-1.24	Destabilizing	0.978	D	0.792	deleterious	None	None	None	None	I

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.