TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9321	28186;28187;28188	chr2:178711275;178711274;178711273	chr2:179576002;179576001;179576000
N2AB	9004	27235;27236;27237	chr2:178711275;178711274;178711273	chr2:179576002;179576001;179576000
N2A	8077	24454;24455;24456	chr2:178711275;178711274;178711273	chr2:179576002;179576001;179576000
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-79
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.4189
• 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
D/Y	rs762498001	0.282	0.859	None	0.732	0.368	0.802398120638	gnomAD-4.0.0	4.77797E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.31072E-05	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	0.1897	likely_benign	0.2046	benign	-0.497	Destabilizing	0.124	N	0.568	neutral	None	None	None	None	N
D/C	0.6799	likely_pathogenic	0.7066	pathogenic	-0.183	Destabilizing	0.968	D	0.739	prob.delet.	None	None	None	None	N
D/E	0.1381	likely_benign	0.1537	benign	-0.769	Destabilizing	None	N	0.237	neutral	None	None	None	None	N
D/F	0.607	likely_pathogenic	0.6039	pathogenic	-0.11	Destabilizing	0.89	D	0.731	prob.delet.	None	None	None	None	N
D/G	0.2208	likely_benign	0.2384	benign	-0.86	Destabilizing	0.22	N	0.491	neutral	None	None	None	None	N
D/H	0.2079	likely_benign	0.2322	benign	-0.429	Destabilizing	0.667	D	0.658	neutral	None	None	None	None	N
D/I	0.3654	ambiguous	0.3816	ambiguous	0.464	Stabilizing	0.726	D	0.716	prob.delet.	None	None	None	None	N
D/K	0.2864	likely_benign	0.3231	benign	-0.304	Destabilizing	0.157	N	0.486	neutral	None	None	None	None	N
D/L	0.3819	ambiguous	0.3982	ambiguous	0.464	Stabilizing	0.567	D	0.663	neutral	None	None	None	None	N
D/M	0.6435	likely_pathogenic	0.6714	pathogenic	0.893	Stabilizing	0.968	D	0.727	prob.delet.	None	None	None	None	N
D/N	0.1048	likely_benign	0.1111	benign	-0.792	Destabilizing	0.22	N	0.438	neutral	None	None	None	None	N
D/P	0.8172	likely_pathogenic	0.8545	pathogenic	0.17	Stabilizing	0.726	D	0.608	neutral	None	None	None	None	N
D/Q	0.2345	likely_benign	0.277	benign	-0.644	Destabilizing	0.157	N	0.443	neutral	None	None	None	None	N
D/R	0.2885	likely_benign	0.3209	benign	-0.152	Destabilizing	0.396	N	0.649	neutral	None	None	None	None	N
D/S	0.1117	likely_benign	0.1148	benign	-1.038	Destabilizing	0.157	N	0.427	neutral	None	None	None	None	N
D/T	0.1963	likely_benign	0.2138	benign	-0.736	Destabilizing	0.272	N	0.533	neutral	None	None	None	None	N
D/V	0.2249	likely_benign	0.2403	benign	0.17	Stabilizing	0.497	N	0.665	neutral	None	None	None	None	N
D/W	0.8776	likely_pathogenic	0.8924	pathogenic	0.061	Stabilizing	0.968	D	0.705	prob.neutral	None	None	None	None	N
D/Y	0.2552	likely_benign	0.258	benign	0.142	Stabilizing	0.859	D	0.732	prob.delet.	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.