TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19035	57328;57329;57330	chr2:178598514;178598513;178598512	chr2:179463241;179463240;179463239
N2AB	17394	52405;52406;52407	chr2:178598514;178598513;178598512	chr2:179463241;179463240;179463239
N2A	16467	49624;49625;49626	chr2:178598514;178598513;178598512	chr2:179463241;179463240;179463239
N2B	9970	30133;30134;30135	chr2:178598514;178598513;178598512	chr2:179463241;179463240;179463239
Novex-1	10095	30508;30509;30510	chr2:178598514;178598513;178598512	chr2:179463241;179463240;179463239
Novex-2	10162	30709;30710;30711	chr2:178598514;178598513;178598512	chr2:179463241;179463240;179463239
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Fn3-26
• Domain position: 48
• Structural Position: 65
• Q(SASA): 0.2398
• 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
W/R	None	None	0.994	D	0.674	0.33	0.540743726455	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
W/A	0.9782	likely_pathogenic	0.9831	pathogenic	-3.094	Highly Destabilizing	0.985	D	0.577	neutral	None	None	None	None	N
W/C	0.9953	likely_pathogenic	0.9965	pathogenic	-1.247	Destabilizing	1.0	D	0.681	prob.neutral	D	0.53454264	None	None	N
W/D	0.9908	likely_pathogenic	0.9925	pathogenic	-1.949	Destabilizing	0.971	D	0.575	neutral	None	None	None	None	N
W/E	0.9918	likely_pathogenic	0.9941	pathogenic	-1.883	Destabilizing	0.469	N	0.397	neutral	None	None	None	None	N
W/F	0.7528	likely_pathogenic	0.7788	pathogenic	-1.91	Destabilizing	0.999	D	0.571	neutral	None	None	None	None	N
W/G	0.9325	likely_pathogenic	0.9416	pathogenic	-3.277	Highly Destabilizing	0.99	D	0.545	neutral	N	0.506777146	None	None	N
W/H	0.9936	likely_pathogenic	0.9953	pathogenic	-1.566	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
W/I	0.9743	likely_pathogenic	0.982	pathogenic	-2.417	Highly Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
W/K	0.9984	likely_pathogenic	0.9987	pathogenic	-1.586	Destabilizing	0.996	D	0.593	neutral	None	None	None	None	N
W/L	0.9554	likely_pathogenic	0.9612	pathogenic	-2.417	Highly Destabilizing	0.99	D	0.543	neutral	N	0.505763188	None	None	N
W/M	0.9812	likely_pathogenic	0.9867	pathogenic	-1.796	Destabilizing	1.0	D	0.567	neutral	None	None	None	None	N
W/N	0.9938	likely_pathogenic	0.995	pathogenic	-1.898	Destabilizing	0.998	D	0.673	neutral	None	None	None	None	N
W/P	0.9885	likely_pathogenic	0.9917	pathogenic	-2.66	Highly Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
W/Q	0.998	likely_pathogenic	0.9987	pathogenic	-1.953	Destabilizing	0.996	D	0.624	neutral	None	None	None	None	N
W/R	0.9978	likely_pathogenic	0.9982	pathogenic	-0.934	Destabilizing	0.994	D	0.674	neutral	D	0.522261282	None	None	N
W/S	0.9774	likely_pathogenic	0.9823	pathogenic	-2.311	Highly Destabilizing	0.994	D	0.6	neutral	D	0.532768213	None	None	N
W/T	0.9738	likely_pathogenic	0.9814	pathogenic	-2.201	Highly Destabilizing	0.998	D	0.559	neutral	None	None	None	None	N
W/V	0.9738	likely_pathogenic	0.9811	pathogenic	-2.66	Highly Destabilizing	0.998	D	0.657	neutral	None	None	None	None	N
W/Y	0.8846	likely_pathogenic	0.893	pathogenic	-1.677	Destabilizing	0.999	D	0.519	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.