TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20793	62602;62603;62604	chr2:178589348;178589347;178589346	chr2:179454075;179454074;179454073
N2AB	19152	57679;57680;57681	chr2:178589348;178589347;178589346	chr2:179454075;179454074;179454073
N2A	18225	54898;54899;54900	chr2:178589348;178589347;178589346	chr2:179454075;179454074;179454073
N2B	11728	35407;35408;35409	chr2:178589348;178589347;178589346	chr2:179454075;179454074;179454073
Novex-1	11853	35782;35783;35784	chr2:178589348;178589347;178589346	chr2:179454075;179454074;179454073
Novex-2	11920	35983;35984;35985	chr2:178589348;178589347;178589346	chr2:179454075;179454074;179454073
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-122
• Domain position: 25
• Structural Position: 35
• Q(SASA): 0.2131
• 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	0.454	N	0.613	0.175	0.502752565406	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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	0.7492	likely_pathogenic	0.7536	pathogenic	-1.672	Destabilizing	0.625	D	0.672	neutral	N	0.507286813	None	None	N
V/C	0.8476	likely_pathogenic	0.8831	pathogenic	-1.229	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
V/D	0.9941	likely_pathogenic	0.9949	pathogenic	-1.51	Destabilizing	0.989	D	0.83	deleterious	D	0.62058997	None	None	N
V/E	0.9765	likely_pathogenic	0.9806	pathogenic	-1.408	Destabilizing	0.991	D	0.799	deleterious	None	None	None	None	N
V/F	0.4278	ambiguous	0.4464	ambiguous	-1.082	Destabilizing	0.934	D	0.789	deleterious	D	0.540846771	None	None	N
V/G	0.8446	likely_pathogenic	0.8413	pathogenic	-2.107	Highly Destabilizing	0.966	D	0.789	deleterious	D	0.5671921	None	None	N
V/H	0.982	likely_pathogenic	0.9867	pathogenic	-1.738	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
V/I	0.068	likely_benign	0.0778	benign	-0.526	Destabilizing	0.454	N	0.613	neutral	N	0.495701595	None	None	N
V/K	0.9727	likely_pathogenic	0.9771	pathogenic	-1.242	Destabilizing	0.974	D	0.785	deleterious	None	None	None	None	N
V/L	0.2175	likely_benign	0.2857	benign	-0.526	Destabilizing	0.005	N	0.239	neutral	D	0.559107416	None	None	N
V/M	0.313	likely_benign	0.3853	ambiguous	-0.534	Destabilizing	0.949	D	0.698	prob.neutral	None	None	None	None	N
V/N	0.9651	likely_pathogenic	0.9752	pathogenic	-1.204	Destabilizing	0.991	D	0.829	deleterious	None	None	None	None	N
V/P	0.9716	likely_pathogenic	0.9768	pathogenic	-0.875	Destabilizing	0.991	D	0.801	deleterious	None	None	None	None	N
V/Q	0.9535	likely_pathogenic	0.9621	pathogenic	-1.222	Destabilizing	0.991	D	0.799	deleterious	None	None	None	None	N
V/R	0.959	likely_pathogenic	0.963	pathogenic	-0.957	Destabilizing	0.974	D	0.833	deleterious	None	None	None	None	N
V/S	0.8999	likely_pathogenic	0.9094	pathogenic	-1.858	Destabilizing	0.974	D	0.79	deleterious	None	None	None	None	N
V/T	0.7776	likely_pathogenic	0.8041	pathogenic	-1.623	Destabilizing	0.915	D	0.703	prob.neutral	None	None	None	None	N
V/W	0.9632	likely_pathogenic	0.9715	pathogenic	-1.397	Destabilizing	0.037	N	0.583	neutral	None	None	None	None	N
V/Y	0.8992	likely_pathogenic	0.9134	pathogenic	-1.042	Destabilizing	0.949	D	0.789	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.