TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14447	43564;43565;43566	chr2:178632667;178632666;178632665	chr2:179497394;179497393;179497392
N2AB	12806	38641;38642;38643	chr2:178632667;178632666;178632665	chr2:179497394;179497393;179497392
N2A	11879	35860;35861;35862	chr2:178632667;178632666;178632665	chr2:179497394;179497393;179497392
N2B	5382	16369;16370;16371	chr2:178632667;178632666;178632665	chr2:179497394;179497393;179497392
Novex-1	5507	16744;16745;16746	chr2:178632667;178632666;178632665	chr2:179497394;179497393;179497392
Novex-2	5574	16945;16946;16947	chr2:178632667;178632666;178632665	chr2:179497394;179497393;179497392
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-95
• Domain position: 40
• Structural Position: 58
• Q(SASA): 0.148
• 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
I/V	rs762998380	-1.072	0.19	N	0.398	0.119	0.541239005379	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.96E-06	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
I/A	0.7901	likely_pathogenic	0.7687	pathogenic	-2.296	Highly Destabilizing	0.633	D	0.61	neutral	None	None	None	None	N
I/C	0.8882	likely_pathogenic	0.8702	pathogenic	-1.52	Destabilizing	0.996	D	0.689	prob.neutral	None	None	None	None	N
I/D	0.9623	likely_pathogenic	0.9579	pathogenic	-2.472	Highly Destabilizing	0.987	D	0.779	deleterious	None	None	None	None	N
I/E	0.918	likely_pathogenic	0.9091	pathogenic	-2.236	Highly Destabilizing	0.961	D	0.763	deleterious	None	None	None	None	N
I/F	0.2655	likely_benign	0.24	benign	-1.375	Destabilizing	0.901	D	0.581	neutral	D	0.569711882	None	None	N
I/G	0.9337	likely_pathogenic	0.9268	pathogenic	-2.842	Highly Destabilizing	0.961	D	0.736	prob.delet.	None	None	None	None	N
I/H	0.8766	likely_pathogenic	0.8594	pathogenic	-2.248	Highly Destabilizing	0.996	D	0.761	deleterious	None	None	None	None	N
I/K	0.8043	likely_pathogenic	0.7884	pathogenic	-1.687	Destabilizing	0.923	D	0.729	prob.delet.	None	None	None	None	N
I/L	0.1365	likely_benign	0.1379	benign	-0.721	Destabilizing	0.003	N	0.156	neutral	N	0.395268355	None	None	N
I/M	0.1287	likely_benign	0.1245	benign	-0.656	Destabilizing	0.075	N	0.385	neutral	N	0.517541184	None	None	N
I/N	0.6887	likely_pathogenic	0.6786	pathogenic	-2.035	Highly Destabilizing	0.949	D	0.779	deleterious	D	0.612979889	None	None	N
I/P	0.9614	likely_pathogenic	0.9621	pathogenic	-1.226	Destabilizing	0.987	D	0.782	deleterious	None	None	None	None	N
I/Q	0.8548	likely_pathogenic	0.8412	pathogenic	-1.878	Destabilizing	0.961	D	0.779	deleterious	None	None	None	None	N
I/R	0.7426	likely_pathogenic	0.7178	pathogenic	-1.498	Destabilizing	0.923	D	0.781	deleterious	None	None	None	None	N
I/S	0.8158	likely_pathogenic	0.7999	pathogenic	-2.737	Highly Destabilizing	0.901	D	0.697	prob.neutral	D	0.612065664	None	None	N
I/T	0.7561	likely_pathogenic	0.7318	pathogenic	-2.341	Highly Destabilizing	0.722	D	0.646	neutral	D	0.606626239	None	None	N
I/V	0.1475	likely_benign	0.139	benign	-1.226	Destabilizing	0.19	N	0.398	neutral	N	0.490622904	None	None	N
I/W	0.8923	likely_pathogenic	0.8724	pathogenic	-1.72	Destabilizing	0.996	D	0.771	deleterious	None	None	None	None	N
I/Y	0.6999	likely_pathogenic	0.6783	pathogenic	-1.394	Destabilizing	0.961	D	0.738	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.