TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1857	5794;5795;5796	chr2:178776295;178776294;178776293	chr2:179641022;179641021;179641020
N2AB	1857	5794;5795;5796	chr2:178776295;178776294;178776293	chr2:179641022;179641021;179641020
N2A	1857	5794;5795;5796	chr2:178776295;178776294;178776293	chr2:179641022;179641021;179641020
N2B	1811	5656;5657;5658	chr2:178776295;178776294;178776293	chr2:179641022;179641021;179641020
Novex-1	1811	5656;5657;5658	chr2:178776295;178776294;178776293	chr2:179641022;179641021;179641020
Novex-2	1811	5656;5657;5658	chr2:178776295;178776294;178776293	chr2:179641022;179641021;179641020
Novex-3	1857	5794;5795;5796	chr2:178776295;178776294;178776293	chr2:179641022;179641021;179641020

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-9
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.411
• 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/N	None	None	0.995	N	0.448	0.276	0.395745362164	gnomAD-4.0.0	1.59067E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85659E-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	0.1635	likely_benign	0.156	benign	-0.7	Destabilizing	0.78	D	0.364	neutral	N	0.514335542	None	None	N
T/C	0.7373	likely_pathogenic	0.7451	pathogenic	-0.382	Destabilizing	0.999	D	0.537	neutral	None	None	None	None	N
T/D	0.8358	likely_pathogenic	0.8077	pathogenic	-0.412	Destabilizing	0.996	D	0.466	neutral	None	None	None	None	N
T/E	0.7411	likely_pathogenic	0.6911	pathogenic	-0.433	Destabilizing	0.996	D	0.455	neutral	None	None	None	None	N
T/F	0.6674	likely_pathogenic	0.6568	pathogenic	-0.8	Destabilizing	0.976	D	0.573	neutral	None	None	None	None	N
T/G	0.4662	ambiguous	0.4425	ambiguous	-0.942	Destabilizing	0.996	D	0.467	neutral	None	None	None	None	N
T/H	0.6575	likely_pathogenic	0.6239	pathogenic	-1.238	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
T/I	0.3803	ambiguous	0.3578	ambiguous	-0.15	Destabilizing	0.011	N	0.21	neutral	N	0.511816535	None	None	N
T/K	0.6586	likely_pathogenic	0.6073	pathogenic	-0.812	Destabilizing	0.988	D	0.462	neutral	None	None	None	None	N
T/L	0.2513	likely_benign	0.244	benign	-0.15	Destabilizing	0.702	D	0.403	neutral	None	None	None	None	N
T/M	0.1504	likely_benign	0.1496	benign	0.213	Stabilizing	0.976	D	0.543	neutral	None	None	None	None	N
T/N	0.2723	likely_benign	0.2667	benign	-0.675	Destabilizing	0.995	D	0.448	neutral	N	0.514599138	None	None	N
T/P	0.221	likely_benign	0.212	benign	-0.301	Destabilizing	0.995	D	0.511	neutral	N	0.504945413	None	None	N
T/Q	0.5602	ambiguous	0.5282	ambiguous	-0.89	Destabilizing	0.996	D	0.53	neutral	None	None	None	None	N
T/R	0.6171	likely_pathogenic	0.5645	pathogenic	-0.503	Destabilizing	0.996	D	0.53	neutral	None	None	None	None	N
T/S	0.2251	likely_benign	0.2197	benign	-0.903	Destabilizing	0.946	D	0.383	neutral	N	0.502034905	None	None	N
T/V	0.2628	likely_benign	0.2521	benign	-0.301	Destabilizing	0.507	D	0.317	neutral	None	None	None	None	N
T/W	0.9056	likely_pathogenic	0.8976	pathogenic	-0.749	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
T/Y	0.707	likely_pathogenic	0.6944	pathogenic	-0.53	Destabilizing	0.996	D	0.594	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.