TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5460	16603;16604;16605	chr2:178732683;178732682;178732681	chr2:179597410;179597409;179597408
N2AB	5143	15652;15653;15654	chr2:178732683;178732682;178732681	chr2:179597410;179597409;179597408
N2A	4216	12871;12872;12873	chr2:178732683;178732682;178732681	chr2:179597410;179597409;179597408
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-38
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.5513
• Predicted PPI site: I

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
D/G	None	None	0.477	N	0.497	0.314	0.289474373501	gnomAD-4.0.0	1.62005E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.9025E-06	0	0
D/N	rs771075704	-0.023	0.864	N	0.513	0.289	0.331619326243	gnomAD-2.1.1	4.2E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.19E-06	0
D/N	rs771075704	-0.023	0.864	N	0.513	0.289	0.331619326243	gnomAD-4.0.0	1.62156E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.905E-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
D/A	0.1325	likely_benign	0.1504	benign	-0.274	Destabilizing	0.006	N	0.329	neutral	N	0.446419208	None	None	I
D/C	0.6259	likely_pathogenic	0.6902	pathogenic	-0.194	Destabilizing	0.985	D	0.684	prob.neutral	None	None	None	None	I
D/E	0.1152	likely_benign	0.1278	benign	-0.278	Destabilizing	0.006	N	0.168	neutral	N	0.375191041	None	None	I
D/F	0.506	ambiguous	0.5628	ambiguous	0.289	Stabilizing	0.945	D	0.673	neutral	None	None	None	None	I
D/G	0.1858	likely_benign	0.2204	benign	-0.57	Destabilizing	0.477	N	0.497	neutral	N	0.517570017	None	None	I
D/H	0.2611	likely_benign	0.2988	benign	0.423	Stabilizing	0.98	D	0.524	neutral	N	0.466834552	None	None	I
D/I	0.2478	likely_benign	0.2866	benign	0.49	Stabilizing	0.894	D	0.667	neutral	None	None	None	None	I
D/K	0.3244	likely_benign	0.3786	ambiguous	0.211	Stabilizing	0.547	D	0.505	neutral	None	None	None	None	I
D/L	0.3001	likely_benign	0.3417	ambiguous	0.49	Stabilizing	0.809	D	0.643	neutral	None	None	None	None	I
D/M	0.4518	ambiguous	0.5094	ambiguous	0.531	Stabilizing	0.985	D	0.646	neutral	None	None	None	None	I
D/N	0.1031	likely_benign	0.1151	benign	-0.435	Destabilizing	0.864	D	0.513	neutral	N	0.438397157	None	None	I
D/P	0.6201	likely_pathogenic	0.6778	pathogenic	0.26	Stabilizing	0.945	D	0.55	neutral	None	None	None	None	I
D/Q	0.2686	likely_benign	0.3042	benign	-0.305	Destabilizing	0.809	D	0.523	neutral	None	None	None	None	I
D/R	0.3637	ambiguous	0.4142	ambiguous	0.521	Stabilizing	0.894	D	0.64	neutral	None	None	None	None	I
D/S	0.1351	likely_benign	0.1506	benign	-0.571	Destabilizing	0.547	D	0.491	neutral	None	None	None	None	I
D/T	0.1811	likely_benign	0.2073	benign	-0.314	Destabilizing	0.894	D	0.5	neutral	None	None	None	None	I
D/V	0.1311	likely_benign	0.1463	benign	0.26	Stabilizing	0.761	D	0.597	neutral	N	0.429852245	None	None	I
D/W	0.8192	likely_pathogenic	0.8512	pathogenic	0.542	Stabilizing	0.995	D	0.691	prob.neutral	None	None	None	None	I
D/Y	0.177	likely_benign	0.1981	benign	0.568	Stabilizing	0.993	D	0.67	neutral	N	0.482900083	None	None	I

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.