TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	954	3085;3086;3087	chr2:178783046;178783045;178783044	chr2:179647773;179647772;179647771
N2AB	954	3085;3086;3087	chr2:178783046;178783045;178783044	chr2:179647773;179647772;179647771
N2A	954	3085;3086;3087	chr2:178783046;178783045;178783044	chr2:179647773;179647772;179647771
N2B	908	2947;2948;2949	chr2:178783046;178783045;178783044	chr2:179647773;179647772;179647771
Novex-1	908	2947;2948;2949	chr2:178783046;178783045;178783044	chr2:179647773;179647772;179647771
Novex-2	908	2947;2948;2949	chr2:178783046;178783045;178783044	chr2:179647773;179647772;179647771
Novex-3	954	3085;3086;3087	chr2:178783046;178783045;178783044	chr2:179647773;179647772;179647771

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-3
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1989
• 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
V/G	None	None	1.0	D	0.677	0.767	0.9214070867	gnomAD-4.0.0	1.5906E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85667E-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
V/A	0.7523	likely_pathogenic	0.7501	pathogenic	-1.825	Destabilizing	0.999	D	0.447	neutral	N	0.492426001	None	None	N
V/C	0.9772	likely_pathogenic	0.9734	pathogenic	-1.399	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	N
V/D	0.9953	likely_pathogenic	0.9959	pathogenic	-1.984	Destabilizing	1.0	D	0.686	prob.neutral	D	0.763862971	None	None	N
V/E	0.9745	likely_pathogenic	0.9757	pathogenic	-1.926	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
V/F	0.9435	likely_pathogenic	0.9412	pathogenic	-1.283	Destabilizing	1.0	D	0.689	prob.neutral	D	0.5992337679999999	None	None	N
V/G	0.9141	likely_pathogenic	0.9165	pathogenic	-2.203	Highly Destabilizing	1.0	D	0.677	prob.neutral	D	0.603553618	None	None	N
V/H	0.9957	likely_pathogenic	0.9954	pathogenic	-1.737	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	N
V/I	0.2153	likely_benign	0.221	benign	-0.851	Destabilizing	0.997	D	0.47	neutral	N	0.515885699	None	None	N
V/K	0.9695	likely_pathogenic	0.9703	pathogenic	-1.549	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	N
V/L	0.8594	likely_pathogenic	0.8532	pathogenic	-0.851	Destabilizing	0.997	D	0.483	neutral	D	0.523217805	None	None	N
V/M	0.7666	likely_pathogenic	0.7594	pathogenic	-0.786	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
V/N	0.9867	likely_pathogenic	0.9866	pathogenic	-1.484	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
V/P	0.9982	likely_pathogenic	0.9982	pathogenic	-1.143	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
V/Q	0.9696	likely_pathogenic	0.9696	pathogenic	-1.6	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
V/R	0.9564	likely_pathogenic	0.9564	pathogenic	-1.07	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
V/S	0.9311	likely_pathogenic	0.931	pathogenic	-2.04	Highly Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
V/T	0.7732	likely_pathogenic	0.7685	pathogenic	-1.87	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	N
V/W	0.9992	likely_pathogenic	0.9991	pathogenic	-1.547	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	N
V/Y	0.9952	likely_pathogenic	0.9949	pathogenic	-1.246	Destabilizing	1.0	D	0.687	prob.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.