TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6406	19441;19442;19443	chr2:178728710;178728709;178728708	chr2:179593437;179593436;179593435
N2AB	6089	18490;18491;18492	chr2:178728710;178728709;178728708	chr2:179593437;179593436;179593435
N2A	5162	15709;15710;15711	chr2:178728710;178728709;178728708	chr2:179593437;179593436;179593435
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: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-48
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0686
• 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
C/Y	None	None	1.0	D	0.943	0.58	0.807043397782	gnomAD-4.0.0	1.59331E-06	None	None	None	None	N	None	0	0	None	0	2.77608E-05	None	0	0	0	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
C/A	0.8422	likely_pathogenic	0.8466	pathogenic	-1.641	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
C/D	0.9977	likely_pathogenic	0.998	pathogenic	-1.517	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
C/E	0.9987	likely_pathogenic	0.9988	pathogenic	-1.266	Destabilizing	1.0	D	0.941	deleterious	None	None	None	None	N
C/F	0.5972	likely_pathogenic	0.5586	ambiguous	-0.996	Destabilizing	1.0	D	0.931	deleterious	D	0.558787231	None	None	N
C/G	0.6897	likely_pathogenic	0.6718	pathogenic	-2.023	Highly Destabilizing	1.0	D	0.911	deleterious	D	0.540682976	None	None	N
C/H	0.9909	likely_pathogenic	0.9904	pathogenic	-2.249	Highly Destabilizing	1.0	D	0.937	deleterious	None	None	None	None	N
C/I	0.8603	likely_pathogenic	0.8279	pathogenic	-0.6	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
C/K	0.9991	likely_pathogenic	0.9991	pathogenic	-1.055	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
C/L	0.8626	likely_pathogenic	0.8469	pathogenic	-0.6	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
C/M	0.902	likely_pathogenic	0.8926	pathogenic	0.288	Stabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
C/N	0.9853	likely_pathogenic	0.9858	pathogenic	-1.737	Destabilizing	1.0	D	0.939	deleterious	None	None	None	None	N
C/P	0.999	likely_pathogenic	0.9992	pathogenic	-0.924	Destabilizing	1.0	D	0.939	deleterious	None	None	None	None	N
C/Q	0.997	likely_pathogenic	0.9971	pathogenic	-1.224	Destabilizing	1.0	D	0.951	deleterious	None	None	None	None	N
C/R	0.9925	likely_pathogenic	0.9927	pathogenic	-1.525	Destabilizing	1.0	D	0.944	deleterious	D	0.55904072	None	None	N
C/S	0.9126	likely_pathogenic	0.9082	pathogenic	-2.034	Highly Destabilizing	1.0	D	0.837	deleterious	D	0.52932667	None	None	N
C/T	0.9224	likely_pathogenic	0.9171	pathogenic	-1.585	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
C/V	0.7066	likely_pathogenic	0.6742	pathogenic	-0.924	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
C/W	0.957	likely_pathogenic	0.9559	pathogenic	-1.398	Destabilizing	1.0	D	0.924	deleterious	D	0.55904072	None	None	N
C/Y	0.7792	likely_pathogenic	0.7697	pathogenic	-1.193	Destabilizing	1.0	D	0.943	deleterious	D	0.52455373	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.