TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35729	107410;107411;107412	chr2:178528566;178528565;178528564	chr2:179393293;179393292;179393291
N2AB	34088	102487;102488;102489	chr2:178528566;178528565;178528564	chr2:179393293;179393292;179393291
N2A	33161	99706;99707;99708	chr2:178528566;178528565;178528564	chr2:179393293;179393292;179393291
N2B	26664	80215;80216;80217	chr2:178528566;178528565;178528564	chr2:179393293;179393292;179393291
Novex-1	26789	80590;80591;80592	chr2:178528566;178528565;178528564	chr2:179393293;179393292;179393291
Novex-2	26856	80791;80792;80793	chr2:178528566;178528565;178528564	chr2:179393293;179393292;179393291
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-168
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.4583
• 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
P/S	None	None	1.0	D	0.748	0.815	0.65692934574	gnomAD-4.0.0	1.59631E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86824E-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
P/A	0.5128	ambiguous	0.5352	ambiguous	-1.074	Destabilizing	1.0	D	0.73	prob.delet.	D	0.543187051	None	None	I
P/C	0.9644	likely_pathogenic	0.9756	pathogenic	-0.709	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
P/D	0.9084	likely_pathogenic	0.9149	pathogenic	-0.64	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
P/E	0.8405	likely_pathogenic	0.8435	pathogenic	-0.689	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
P/F	0.9498	likely_pathogenic	0.9611	pathogenic	-0.98	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
P/G	0.8605	likely_pathogenic	0.8783	pathogenic	-1.314	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
P/H	0.8437	likely_pathogenic	0.8502	pathogenic	-0.8	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
P/I	0.8202	likely_pathogenic	0.8481	pathogenic	-0.546	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
P/K	0.8945	likely_pathogenic	0.8969	pathogenic	-0.837	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
P/L	0.6423	likely_pathogenic	0.675	pathogenic	-0.546	Destabilizing	1.0	D	0.763	deleterious	D	0.616421724	None	None	I
P/M	0.8541	likely_pathogenic	0.8726	pathogenic	-0.464	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
P/N	0.8861	likely_pathogenic	0.894	pathogenic	-0.559	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
P/Q	0.7915	likely_pathogenic	0.7877	pathogenic	-0.75	Destabilizing	1.0	D	0.766	deleterious	D	0.569685097	None	None	I
P/R	0.8127	likely_pathogenic	0.8117	pathogenic	-0.306	Destabilizing	1.0	D	0.788	deleterious	D	0.648289003	None	None	I
P/S	0.7665	likely_pathogenic	0.7756	pathogenic	-1.024	Destabilizing	1.0	D	0.748	deleterious	D	0.548605101	None	None	I
P/T	0.6141	likely_pathogenic	0.6205	pathogenic	-0.962	Destabilizing	1.0	D	0.743	deleterious	D	0.616018116	None	None	I
P/V	0.7149	likely_pathogenic	0.7508	pathogenic	-0.686	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	I
P/W	0.9783	likely_pathogenic	0.9824	pathogenic	-1.098	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
P/Y	0.9271	likely_pathogenic	0.9417	pathogenic	-0.813	Destabilizing	1.0	D	0.815	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.