TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33762	101509;101510;101511	chr2:178535331;178535330;178535329	chr2:179400058;179400057;179400056
N2AB	32121	96586;96587;96588	chr2:178535331;178535330;178535329	chr2:179400058;179400057;179400056
N2A	31194	93805;93806;93807	chr2:178535331;178535330;178535329	chr2:179400058;179400057;179400056
N2B	24697	74314;74315;74316	chr2:178535331;178535330;178535329	chr2:179400058;179400057;179400056
Novex-1	24822	74689;74690;74691	chr2:178535331;178535330;178535329	chr2:179400058;179400057;179400056
Novex-2	24889	74890;74891;74892	chr2:178535331;178535330;178535329	chr2:179400058;179400057;179400056
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-132
• Domain position: 74
• Structural Position: 108
• Q(SASA): 0.0743
• 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	rs1385559568	None	0.003	N	0.203	0.151	0.433047596574	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs1385559568	None	0.003	N	0.203	0.151	0.433047596574	gnomAD-4.0.0	2.47863E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39026E-06	0	0
V/L	rs1385559568	None	0.001	N	0.321	0.311	0.532359089423	gnomAD-4.0.0	1.36837E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79886E-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	0.9373	likely_pathogenic	0.9581	pathogenic	-2.516	Highly Destabilizing	0.675	D	0.571	neutral	D	0.567292014	None	None	N
V/C	0.9686	likely_pathogenic	0.9787	pathogenic	-1.917	Destabilizing	0.996	D	0.743	deleterious	None	None	None	None	N
V/D	0.9986	likely_pathogenic	0.9991	pathogenic	-3.457	Highly Destabilizing	0.999	D	0.905	deleterious	None	None	None	None	N
V/E	0.9964	likely_pathogenic	0.9975	pathogenic	-3.15	Highly Destabilizing	0.995	D	0.853	deleterious	D	0.629019336	None	None	N
V/F	0.9506	likely_pathogenic	0.9492	pathogenic	-1.376	Destabilizing	0.947	D	0.734	prob.delet.	None	None	None	None	N
V/G	0.9643	likely_pathogenic	0.9757	pathogenic	-3.096	Highly Destabilizing	0.98	D	0.883	deleterious	D	0.629019336	None	None	N
V/H	0.9992	likely_pathogenic	0.9995	pathogenic	-2.932	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
V/I	0.1216	likely_benign	0.1146	benign	-0.822	Destabilizing	0.003	N	0.203	neutral	N	0.503491572	None	None	N
V/K	0.9976	likely_pathogenic	0.9985	pathogenic	-2.024	Highly Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
V/L	0.8	likely_pathogenic	0.8123	pathogenic	-0.822	Destabilizing	0.001	N	0.321	neutral	N	0.498554616	None	None	N
V/M	0.8773	likely_pathogenic	0.8859	pathogenic	-1.095	Destabilizing	0.928	D	0.633	neutral	None	None	None	None	N
V/N	0.9941	likely_pathogenic	0.9966	pathogenic	-2.66	Highly Destabilizing	0.996	D	0.912	deleterious	None	None	None	None	N
V/P	0.9962	likely_pathogenic	0.998	pathogenic	-1.371	Destabilizing	0.996	D	0.87	deleterious	None	None	None	None	N
V/Q	0.9968	likely_pathogenic	0.9978	pathogenic	-2.326	Highly Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
V/R	0.9953	likely_pathogenic	0.9968	pathogenic	-2.048	Highly Destabilizing	0.999	D	0.911	deleterious	None	None	None	None	N
V/S	0.9829	likely_pathogenic	0.9895	pathogenic	-3.153	Highly Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
V/T	0.9521	likely_pathogenic	0.9693	pathogenic	-2.702	Highly Destabilizing	0.972	D	0.599	neutral	None	None	None	None	N
V/W	0.9994	likely_pathogenic	0.9994	pathogenic	-1.959	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/Y	0.9966	likely_pathogenic	0.9967	pathogenic	-1.681	Destabilizing	0.999	D	0.723	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.