TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9090	27493;27494;27495	chr2:178712757;178712756;178712755	chr2:179577484;179577483;179577482
N2AB	8773	26542;26543;26544	chr2:178712757;178712756;178712755	chr2:179577484;179577483;179577482
N2A	7846	23761;23762;23763	chr2:178712757;178712756;178712755	chr2:179577484;179577483;179577482
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: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-76
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1764
• 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	None	None	0.811	N	0.595	0.358	0.503248607038	gnomAD-4.0.0	4.77376E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57452E-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	0.1157	likely_benign	0.1292	benign	-1.174	Destabilizing	0.64	D	0.51	neutral	N	0.490449501	None	None	N
T/C	0.5801	likely_pathogenic	0.664	pathogenic	-0.711	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	N
T/D	0.6097	likely_pathogenic	0.7241	pathogenic	-1.414	Destabilizing	0.919	D	0.59	neutral	None	None	None	None	N
T/E	0.4796	ambiguous	0.5849	pathogenic	-1.206	Destabilizing	0.919	D	0.587	neutral	None	None	None	None	N
T/F	0.3221	likely_benign	0.4147	ambiguous	-0.921	Destabilizing	0.988	D	0.676	prob.neutral	None	None	None	None	N
T/G	0.3998	ambiguous	0.4524	ambiguous	-1.579	Destabilizing	0.851	D	0.629	neutral	None	None	None	None	N
T/H	0.3041	likely_benign	0.3634	ambiguous	-1.682	Destabilizing	0.999	D	0.682	prob.neutral	None	None	None	None	N
T/I	0.2353	likely_benign	0.2853	benign	-0.105	Destabilizing	0.811	D	0.595	neutral	N	0.471344515	None	None	N
T/K	0.2999	likely_benign	0.3739	ambiguous	-0.214	Destabilizing	0.919	D	0.594	neutral	None	None	None	None	N
T/L	0.1569	likely_benign	0.1843	benign	-0.105	Destabilizing	0.702	D	0.614	neutral	None	None	None	None	N
T/M	0.1241	likely_benign	0.1294	benign	-0.138	Destabilizing	0.988	D	0.669	neutral	None	None	None	None	N
T/N	0.2097	likely_benign	0.2623	benign	-0.918	Destabilizing	0.896	D	0.575	neutral	N	0.502984349	None	None	N
T/P	0.75	likely_pathogenic	0.8419	pathogenic	-0.432	Destabilizing	0.984	D	0.621	neutral	D	0.529735884	None	None	N
T/Q	0.3068	likely_benign	0.3544	ambiguous	-0.703	Destabilizing	0.988	D	0.652	neutral	None	None	None	None	N
T/R	0.2044	likely_benign	0.2625	benign	-0.492	Destabilizing	0.976	D	0.643	neutral	None	None	None	None	N
T/S	0.1207	likely_benign	0.1345	benign	-1.157	Destabilizing	0.046	N	0.363	neutral	N	0.470756639	None	None	N
T/V	0.1953	likely_benign	0.2178	benign	-0.432	Destabilizing	0.132	N	0.449	neutral	None	None	None	None	N
T/W	0.6965	likely_pathogenic	0.7851	pathogenic	-1.068	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
T/Y	0.3576	ambiguous	0.4536	ambiguous	-0.664	Destabilizing	0.996	D	0.675	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.