TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29675	89248;89249;89250	chr2:178554088;178554087;178554086	chr2:179418815;179418814;179418813
N2AB	28034	84325;84326;84327	chr2:178554088;178554087;178554086	chr2:179418815;179418814;179418813
N2A	27107	81544;81545;81546	chr2:178554088;178554087;178554086	chr2:179418815;179418814;179418813
N2B	20610	62053;62054;62055	chr2:178554088;178554087;178554086	chr2:179418815;179418814;179418813
Novex-1	20735	62428;62429;62430	chr2:178554088;178554087;178554086	chr2:179418815;179418814;179418813
Novex-2	20802	62629;62630;62631	chr2:178554088;178554087;178554086	chr2:179418815;179418814;179418813
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-104
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.2413
• 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
K/R	None	None	0.999	N	0.598	0.334	0.438806408302	gnomAD-4.0.0	1.59106E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85791E-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
K/A	0.6277	likely_pathogenic	0.7505	pathogenic	-0.726	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	N
K/C	0.8215	likely_pathogenic	0.871	pathogenic	-0.649	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
K/D	0.9035	likely_pathogenic	0.9509	pathogenic	0.064	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/E	0.4162	ambiguous	0.5718	pathogenic	0.162	Stabilizing	0.999	D	0.674	neutral	N	0.517537439	None	None	N
K/F	0.9336	likely_pathogenic	0.9616	pathogenic	-0.514	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
K/G	0.66	likely_pathogenic	0.7719	pathogenic	-1.063	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
K/H	0.5591	ambiguous	0.6507	pathogenic	-1.339	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
K/I	0.6522	likely_pathogenic	0.7528	pathogenic	0.137	Stabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
K/L	0.6235	likely_pathogenic	0.72	pathogenic	0.137	Stabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
K/M	0.4469	ambiguous	0.559	ambiguous	0.051	Stabilizing	1.0	D	0.664	neutral	N	0.477017552	None	None	N
K/N	0.8218	likely_pathogenic	0.9026	pathogenic	-0.35	Destabilizing	1.0	D	0.756	deleterious	N	0.477106457	None	None	N
K/P	0.8988	likely_pathogenic	0.9367	pathogenic	-0.121	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
K/Q	0.2002	likely_benign	0.2639	benign	-0.447	Destabilizing	1.0	D	0.752	deleterious	N	0.476737609	None	None	N
K/R	0.0788	likely_benign	0.0839	benign	-0.49	Destabilizing	0.999	D	0.598	neutral	N	0.51775087	None	None	N
K/S	0.7122	likely_pathogenic	0.8204	pathogenic	-1.077	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
K/T	0.464	ambiguous	0.6095	pathogenic	-0.769	Destabilizing	1.0	D	0.716	prob.delet.	N	0.472727869	None	None	N
K/V	0.5859	likely_pathogenic	0.6897	pathogenic	-0.121	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/W	0.8897	likely_pathogenic	0.9248	pathogenic	-0.341	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
K/Y	0.8598	likely_pathogenic	0.9028	pathogenic	-0.067	Destabilizing	1.0	D	0.717	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.