TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5559	16900;16901;16902	chr2:178732294;178732293;178732292	chr2:179597021;179597020;179597019
N2AB	5242	15949;15950;15951	chr2:178732294;178732293;178732292	chr2:179597021;179597020;179597019
N2A	4315	13168;13169;13170	chr2:178732294;178732293;178732292	chr2:179597021;179597020;179597019
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-39
• Domain position: 17
• Structural Position: 25
• Q(SASA): 0.3055
• 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/V	rs1394384005	None	0.966	N	0.463	0.237	0.488548280593	gnomAD-4.0.0	6.37093E-06	None	None	None	None	N	None	0	0	None	0	1.10926E-04	None	0	0	0	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	0.1214	likely_benign	0.1338	benign	-0.444	Destabilizing	0.454	N	0.362	neutral	N	0.501674192	None	None	N
D/C	0.4553	ambiguous	0.4844	ambiguous	-0.038	Destabilizing	0.998	D	0.461	neutral	None	None	None	None	N
D/E	0.1182	likely_benign	0.1315	benign	-0.489	Destabilizing	0.012	N	0.203	neutral	N	0.40152584	None	None	N
D/F	0.3607	ambiguous	0.3859	ambiguous	-0.215	Destabilizing	0.991	D	0.447	neutral	None	None	None	None	N
D/G	0.1464	likely_benign	0.157	benign	-0.718	Destabilizing	0.005	N	0.154	neutral	N	0.494708147	None	None	N
D/H	0.1983	likely_benign	0.2275	benign	-0.311	Destabilizing	0.966	D	0.351	neutral	N	0.454188085	None	None	N
D/I	0.242	likely_benign	0.2671	benign	0.254	Stabilizing	0.974	D	0.462	neutral	None	None	None	None	N
D/K	0.2556	likely_benign	0.2924	benign	0.119	Stabilizing	0.728	D	0.353	neutral	None	None	None	None	N
D/L	0.2808	likely_benign	0.313	benign	0.254	Stabilizing	0.842	D	0.466	neutral	None	None	None	None	N
D/M	0.3899	ambiguous	0.4233	ambiguous	0.543	Stabilizing	0.998	D	0.435	neutral	None	None	None	None	N
D/N	0.0858	likely_benign	0.0886	benign	-0.328	Destabilizing	0.801	D	0.293	neutral	N	0.498633886	None	None	N
D/P	0.8022	likely_pathogenic	0.8493	pathogenic	0.046	Stabilizing	0.974	D	0.349	neutral	None	None	None	None	N
D/Q	0.2204	likely_benign	0.2537	benign	-0.25	Destabilizing	0.325	N	0.299	neutral	None	None	None	None	N
D/R	0.2913	likely_benign	0.3375	benign	0.261	Stabilizing	0.949	D	0.438	neutral	None	None	None	None	N
D/S	0.1046	likely_benign	0.1084	benign	-0.467	Destabilizing	0.172	N	0.237	neutral	None	None	None	None	N
D/T	0.1829	likely_benign	0.2	benign	-0.244	Destabilizing	0.728	D	0.328	neutral	None	None	None	None	N
D/V	0.1487	likely_benign	0.1643	benign	0.046	Stabilizing	0.966	D	0.463	neutral	N	0.464494433	None	None	N
D/W	0.7472	likely_pathogenic	0.7903	pathogenic	-0.028	Destabilizing	0.998	D	0.521	neutral	None	None	None	None	N
D/Y	0.1424	likely_benign	0.1447	benign	0.039	Stabilizing	0.989	D	0.448	neutral	N	0.51035239	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.