TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32437	97534;97535;97536	chr2:178542447;178542446;178542445	chr2:179407174;179407173;179407172
N2AB	30796	92611;92612;92613	chr2:178542447;178542446;178542445	chr2:179407174;179407173;179407172
N2A	29869	89830;89831;89832	chr2:178542447;178542446;178542445	chr2:179407174;179407173;179407172
N2B	23372	70339;70340;70341	chr2:178542447;178542446;178542445	chr2:179407174;179407173;179407172
Novex-1	23497	70714;70715;70716	chr2:178542447;178542446;178542445	chr2:179407174;179407173;179407172
Novex-2	23564	70915;70916;70917	chr2:178542447;178542446;178542445	chr2:179407174;179407173;179407172
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-124
• Domain position: 39
• Structural Position: 40
• Q(SASA): 0.058
• 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/I	None	None	0.997	N	0.603	0.263	0.66879460378	gnomAD-4.0.0	1.5916E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85871E-06	0	0
V/L	rs2154142556	None	0.997	N	0.635	0.394	0.676840377379	gnomAD-4.0.0	1.5916E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85871E-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	0.6081	likely_pathogenic	0.6302	pathogenic	-2.055	Highly Destabilizing	0.999	D	0.611	neutral	D	0.556454416	None	None	N
V/C	0.9398	likely_pathogenic	0.9514	pathogenic	-1.19	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/D	0.9988	likely_pathogenic	0.999	pathogenic	-2.968	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
V/E	0.9958	likely_pathogenic	0.9964	pathogenic	-2.631	Highly Destabilizing	1.0	D	0.919	deleterious	D	0.56857119	None	None	N
V/F	0.9354	likely_pathogenic	0.9338	pathogenic	-1.1	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
V/G	0.9194	likely_pathogenic	0.928	pathogenic	-2.666	Highly Destabilizing	1.0	D	0.915	deleterious	D	0.56857119	None	None	N
V/H	0.999	likely_pathogenic	0.9992	pathogenic	-2.668	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
V/I	0.1129	likely_benign	0.1029	benign	-0.257	Destabilizing	0.997	D	0.603	neutral	N	0.491972565	None	None	N
V/K	0.9977	likely_pathogenic	0.9979	pathogenic	-1.441	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
V/L	0.5842	likely_pathogenic	0.539	ambiguous	-0.257	Destabilizing	0.997	D	0.635	neutral	N	0.490524494	None	None	N
V/M	0.7337	likely_pathogenic	0.6816	pathogenic	-0.556	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
V/N	0.9954	likely_pathogenic	0.9961	pathogenic	-2.223	Highly Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
V/P	0.9929	likely_pathogenic	0.9944	pathogenic	-0.841	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
V/Q	0.9954	likely_pathogenic	0.9961	pathogenic	-1.785	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
V/R	0.9942	likely_pathogenic	0.9948	pathogenic	-1.799	Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
V/S	0.9442	likely_pathogenic	0.9522	pathogenic	-2.634	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
V/T	0.7667	likely_pathogenic	0.7475	pathogenic	-2.13	Highly Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
V/W	0.9991	likely_pathogenic	0.9991	pathogenic	-1.59	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/Y	0.9963	likely_pathogenic	0.9966	pathogenic	-1.299	Destabilizing	1.0	D	0.861	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.