TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9039	27340;27341;27342	chr2:178712910;178712909;178712908	chr2:179577637;179577636;179577635
N2AB	8722	26389;26390;26391	chr2:178712910;178712909;178712908	chr2:179577637;179577636;179577635
N2A	7795	23608;23609;23610	chr2:178712910;178712909;178712908	chr2:179577637;179577636;179577635
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-76
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.4494
• 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
T/I	rs1560585408	None	0.023	N	0.371	0.34	0.47737504017	gnomAD-4.0.0	1.59269E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85997E-06	0	0
T/R	None	None	0.642	D	0.565	0.281	0.586816528483	gnomAD-4.0.0	1.59269E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85997E-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
T/A	0.101	likely_benign	0.11	benign	-1.097	Destabilizing	0.002	N	0.244	neutral	D	0.533347546	None	None	N
T/C	0.484	ambiguous	0.5119	ambiguous	-0.825	Destabilizing	0.995	D	0.57	neutral	None	None	None	None	N
T/D	0.5163	ambiguous	0.5835	pathogenic	-0.937	Destabilizing	0.543	D	0.502	neutral	None	None	None	None	N
T/E	0.3215	likely_benign	0.3867	ambiguous	-0.867	Destabilizing	0.031	N	0.309	neutral	None	None	None	None	N
T/F	0.2495	likely_benign	0.2886	benign	-0.944	Destabilizing	0.944	D	0.619	neutral	None	None	None	None	N
T/G	0.3543	ambiguous	0.383	ambiguous	-1.423	Destabilizing	0.329	N	0.509	neutral	None	None	None	None	N
T/H	0.2075	likely_benign	0.226	benign	-1.615	Destabilizing	0.944	D	0.625	neutral	None	None	None	None	N
T/I	0.1886	likely_benign	0.2183	benign	-0.293	Destabilizing	0.023	N	0.371	neutral	N	0.500597942	None	None	N
T/K	0.1475	likely_benign	0.1745	benign	-0.911	Destabilizing	0.642	D	0.492	neutral	N	0.510027969	None	None	N
T/L	0.1174	likely_benign	0.1315	benign	-0.293	Destabilizing	0.329	N	0.448	neutral	None	None	None	None	N
T/M	0.1027	likely_benign	0.108	benign	-0.04	Destabilizing	0.944	D	0.574	neutral	None	None	None	None	N
T/N	0.1785	likely_benign	0.192	benign	-1.108	Destabilizing	0.031	N	0.367	neutral	None	None	None	None	N
T/P	0.242	likely_benign	0.3073	benign	-0.529	Destabilizing	0.927	D	0.569	neutral	N	0.490545083	None	None	N
T/Q	0.1951	likely_benign	0.217	benign	-1.197	Destabilizing	0.893	D	0.571	neutral	None	None	None	None	N
T/R	0.1067	likely_benign	0.1259	benign	-0.742	Destabilizing	0.642	D	0.565	neutral	D	0.530192597	None	None	N
T/S	0.1197	likely_benign	0.1219	benign	-1.376	Destabilizing	0.065	N	0.261	neutral	N	0.506795663	None	None	N
T/V	0.1706	likely_benign	0.1873	benign	-0.529	Destabilizing	0.329	N	0.451	neutral	None	None	None	None	N
T/W	0.5585	ambiguous	0.6269	pathogenic	-0.9	Destabilizing	0.995	D	0.655	neutral	None	None	None	None	N
T/Y	0.2723	likely_benign	0.3278	benign	-0.647	Destabilizing	0.981	D	0.615	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.