TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21101	63526;63527;63528	chr2:178588106;178588105;178588104	chr2:179452833;179452832;179452831
N2AB	19460	58603;58604;58605	chr2:178588106;178588105;178588104	chr2:179452833;179452832;179452831
N2A	18533	55822;55823;55824	chr2:178588106;178588105;178588104	chr2:179452833;179452832;179452831
N2B	12036	36331;36332;36333	chr2:178588106;178588105;178588104	chr2:179452833;179452832;179452831
Novex-1	12161	36706;36707;36708	chr2:178588106;178588105;178588104	chr2:179452833;179452832;179452831
Novex-2	12228	36907;36908;36909	chr2:178588106;178588105;178588104	chr2:179452833;179452832;179452831
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-41
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0951
• 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/E	None	None	0.97	D	0.85	0.719	0.882891302514	gnomAD-4.0.0	1.20039E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31257E-06	0	0
V/M	None	None	0.489	N	0.383	0.356	0.557637382247	gnomAD-4.0.0	1.59315E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86157E-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	0.7547	likely_pathogenic	0.7675	pathogenic	-2.282	Highly Destabilizing	0.822	D	0.541	neutral	D	0.535058478	None	None	N
V/C	0.9552	likely_pathogenic	0.9611	pathogenic	-1.555	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
V/D	0.9962	likely_pathogenic	0.9966	pathogenic	-3.257	Highly Destabilizing	0.993	D	0.885	deleterious	None	None	None	None	N
V/E	0.9864	likely_pathogenic	0.9874	pathogenic	-2.92	Highly Destabilizing	0.97	D	0.85	deleterious	D	0.553758618	None	None	N
V/F	0.83	likely_pathogenic	0.8441	pathogenic	-1.281	Destabilizing	0.956	D	0.762	deleterious	None	None	None	None	N
V/G	0.919	likely_pathogenic	0.9277	pathogenic	-2.897	Highly Destabilizing	0.97	D	0.858	deleterious	D	0.553758618	None	None	N
V/H	0.9971	likely_pathogenic	0.9973	pathogenic	-2.876	Highly Destabilizing	0.998	D	0.877	deleterious	None	None	None	None	N
V/I	0.1027	likely_benign	0.0904	benign	-0.471	Destabilizing	0.559	D	0.471	neutral	None	None	None	None	N
V/K	0.9915	likely_pathogenic	0.9912	pathogenic	-1.755	Destabilizing	0.956	D	0.829	deleterious	None	None	None	None	N
V/L	0.3899	ambiguous	0.3679	ambiguous	-0.471	Destabilizing	0.006	N	0.311	neutral	N	0.509870466	None	None	N
V/M	0.5986	likely_pathogenic	0.5889	pathogenic	-0.762	Destabilizing	0.489	N	0.383	neutral	N	0.519182723	None	None	N
V/N	0.9913	likely_pathogenic	0.991	pathogenic	-2.534	Highly Destabilizing	0.978	D	0.885	deleterious	None	None	None	None	N
V/P	0.983	likely_pathogenic	0.9809	pathogenic	-1.059	Destabilizing	0.993	D	0.862	deleterious	None	None	None	None	N
V/Q	0.9877	likely_pathogenic	0.9877	pathogenic	-2.11	Highly Destabilizing	0.978	D	0.872	deleterious	None	None	None	None	N
V/R	0.9824	likely_pathogenic	0.9824	pathogenic	-2.013	Highly Destabilizing	0.978	D	0.887	deleterious	None	None	None	None	N
V/S	0.9592	likely_pathogenic	0.9602	pathogenic	-2.973	Highly Destabilizing	0.956	D	0.812	deleterious	None	None	None	None	N
V/T	0.8314	likely_pathogenic	0.827	pathogenic	-2.471	Highly Destabilizing	0.86	D	0.564	neutral	None	None	None	None	N
V/W	0.9962	likely_pathogenic	0.9963	pathogenic	-1.817	Destabilizing	0.998	D	0.866	deleterious	None	None	None	None	N
V/Y	0.9892	likely_pathogenic	0.9895	pathogenic	-1.532	Destabilizing	0.978	D	0.761	deleterious	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.