TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5819	17680;17681;17682	chr2:178731311;178731310;178731309	chr2:179596038;179596037;179596036
N2AB	5502	16729;16730;16731	chr2:178731311;178731310;178731309	chr2:179596038;179596037;179596036
N2A	4575	13948;13949;13950	chr2:178731311;178731310;178731309	chr2:179596038;179596037;179596036
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: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-41
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.525
• 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	1.0	D	0.86	0.866	0.883693953031	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/I	None	None	0.997	N	0.729	0.486	0.798797874797	gnomAD-4.0.0	1.59169E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85905E-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	0.7913	likely_pathogenic	0.7632	pathogenic	-1.482	Destabilizing	0.999	D	0.761	deleterious	D	0.574871381	None	None	N
V/C	0.96	likely_pathogenic	0.9635	pathogenic	-1.255	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/D	0.9913	likely_pathogenic	0.9912	pathogenic	-0.953	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/E	0.9677	likely_pathogenic	0.9698	pathogenic	-0.952	Destabilizing	1.0	D	0.86	deleterious	D	0.60774768	None	None	N
V/F	0.776	likely_pathogenic	0.819	pathogenic	-1.227	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/G	0.878	likely_pathogenic	0.8684	pathogenic	-1.784	Destabilizing	1.0	D	0.821	deleterious	D	0.60774768	None	None	N
V/H	0.9919	likely_pathogenic	0.9928	pathogenic	-1.236	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
V/I	0.1042	likely_benign	0.108	benign	-0.753	Destabilizing	0.997	D	0.729	prob.delet.	N	0.512334139	None	None	N
V/K	0.9759	likely_pathogenic	0.9794	pathogenic	-1.023	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/L	0.5842	likely_pathogenic	0.6684	pathogenic	-0.753	Destabilizing	0.997	D	0.763	deleterious	D	0.605124225	None	None	N
V/M	0.5773	likely_pathogenic	0.6221	pathogenic	-0.694	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/N	0.9664	likely_pathogenic	0.9671	pathogenic	-0.842	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
V/P	0.9662	likely_pathogenic	0.9648	pathogenic	-0.962	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/Q	0.9637	likely_pathogenic	0.9676	pathogenic	-1.024	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/R	0.9594	likely_pathogenic	0.9645	pathogenic	-0.584	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
V/S	0.9097	likely_pathogenic	0.8934	pathogenic	-1.48	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/T	0.8165	likely_pathogenic	0.7983	pathogenic	-1.363	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
V/W	0.9938	likely_pathogenic	0.995	pathogenic	-1.325	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/Y	0.9804	likely_pathogenic	0.9839	pathogenic	-1.025	Destabilizing	1.0	D	0.885	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.