TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6883	20872;20873;20874	chr2:178725557;178725556;178725555	chr2:179590284;179590283;179590282
N2AB	6566	19921;19922;19923	chr2:178725557;178725556;178725555	chr2:179590284;179590283;179590282
N2A	5639	17140;17141;17142	chr2:178725557;178725556;178725555	chr2:179590284;179590283;179590282
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-53
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1206
• 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
I/M	rs2079192299	None	0.31	N	0.207	0.11	0.416075642716	gnomAD-4.0.0	1.59266E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86053E-06	0	0
I/S	rs1392708886	-2.925	0.959	N	0.529	0.445	0.88295878216	gnomAD-4.0.0	1.36891E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79937E-06	0	0
I/T	None	None	0.959	N	0.485	0.323	0.739771329103	gnomAD-4.0.0	6.84454E-07	None	None	None	None	N	None	0	0	None	0	0	None	1.87336E-05	0	0	0	0
I/V	None	None	0.509	N	0.34	0.17	0.618380283371	gnomAD-4.0.0	1.59273E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02645E-05

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
I/A	0.6918	likely_pathogenic	0.7048	pathogenic	-2.578	Highly Destabilizing	0.863	D	0.44	neutral	None	None	None	None	N
I/C	0.8991	likely_pathogenic	0.884	pathogenic	-1.708	Destabilizing	0.999	D	0.543	neutral	None	None	None	None	N
I/D	0.9724	likely_pathogenic	0.9779	pathogenic	-3.141	Highly Destabilizing	0.997	D	0.601	neutral	None	None	None	None	N
I/E	0.9603	likely_pathogenic	0.9695	pathogenic	-2.868	Highly Destabilizing	0.997	D	0.603	neutral	None	None	None	None	N
I/F	0.3766	ambiguous	0.341	ambiguous	-1.53	Destabilizing	0.92	D	0.518	neutral	N	0.486124083	None	None	N
I/G	0.9359	likely_pathogenic	0.9399	pathogenic	-3.154	Highly Destabilizing	0.991	D	0.607	neutral	None	None	None	None	N
I/H	0.924	likely_pathogenic	0.9335	pathogenic	-2.739	Highly Destabilizing	0.999	D	0.57	neutral	None	None	None	None	N
I/K	0.905	likely_pathogenic	0.9211	pathogenic	-2.027	Highly Destabilizing	0.991	D	0.611	neutral	None	None	None	None	N
I/L	0.1534	likely_benign	0.1415	benign	-0.883	Destabilizing	0.015	N	0.103	neutral	N	0.489207193	None	None	N
I/M	0.2249	likely_benign	0.2097	benign	-0.824	Destabilizing	0.31	N	0.207	neutral	N	0.48398449	None	None	N
I/N	0.7723	likely_pathogenic	0.8058	pathogenic	-2.504	Highly Destabilizing	0.996	D	0.611	neutral	N	0.518560385	None	None	N
I/P	0.8927	likely_pathogenic	0.9042	pathogenic	-1.433	Destabilizing	0.997	D	0.611	neutral	None	None	None	None	N
I/Q	0.9152	likely_pathogenic	0.9271	pathogenic	-2.283	Highly Destabilizing	0.991	D	0.612	neutral	None	None	None	None	N
I/R	0.8402	likely_pathogenic	0.8675	pathogenic	-1.865	Destabilizing	0.991	D	0.598	neutral	None	None	None	None	N
I/S	0.7545	likely_pathogenic	0.7772	pathogenic	-3.139	Highly Destabilizing	0.959	D	0.529	neutral	N	0.500113735	None	None	N
I/T	0.7285	likely_pathogenic	0.7579	pathogenic	-2.717	Highly Destabilizing	0.959	D	0.485	neutral	N	0.495340795	None	None	N
I/V	0.0889	likely_benign	0.0848	benign	-1.433	Destabilizing	0.509	D	0.34	neutral	N	0.490541402	None	None	N
I/W	0.9573	likely_pathogenic	0.9516	pathogenic	-2.008	Highly Destabilizing	0.999	D	0.578	neutral	None	None	None	None	N
I/Y	0.7953	likely_pathogenic	0.7923	pathogenic	-1.692	Destabilizing	0.997	D	0.566	neutral	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.