TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18929	57010;57011;57012	chr2:178598925;178598924;178598923	chr2:179463652;179463651;179463650
N2AB	17288	52087;52088;52089	chr2:178598925;178598924;178598923	chr2:179463652;179463651;179463650
N2A	16361	49306;49307;49308	chr2:178598925;178598924;178598923	chr2:179463652;179463651;179463650
N2B	9864	29815;29816;29817	chr2:178598925;178598924;178598923	chr2:179463652;179463651;179463650
Novex-1	9989	30190;30191;30192	chr2:178598925;178598924;178598923	chr2:179463652;179463651;179463650
Novex-2	10056	30391;30392;30393	chr2:178598925;178598924;178598923	chr2:179463652;179463651;179463650
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: Fn3-25
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.9065
• 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/E	None	None	0.999	N	0.676	0.36	0.323615622048	gnomAD-4.0.0	3.18554E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86015E-06	1.43349E-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
K/A	0.7427	likely_pathogenic	0.7502	pathogenic	-0.05	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
K/C	0.9098	likely_pathogenic	0.9159	pathogenic	-0.512	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
K/D	0.8926	likely_pathogenic	0.8807	pathogenic	-0.317	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
K/E	0.6167	likely_pathogenic	0.645	pathogenic	-0.34	Destabilizing	0.999	D	0.676	prob.neutral	N	0.456390193	None	None	N
K/F	0.9575	likely_pathogenic	0.9645	pathogenic	-0.438	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
K/G	0.7602	likely_pathogenic	0.7444	pathogenic	-0.149	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
K/H	0.6622	likely_pathogenic	0.6597	pathogenic	-0.237	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
K/I	0.73	likely_pathogenic	0.7616	pathogenic	0.127	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
K/L	0.6691	likely_pathogenic	0.687	pathogenic	0.127	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	N
K/M	0.6178	likely_pathogenic	0.6278	pathogenic	-0.155	Destabilizing	1.0	D	0.705	prob.neutral	N	0.516172002	None	None	N
K/N	0.8201	likely_pathogenic	0.8023	pathogenic	-0.055	Destabilizing	1.0	D	0.715	prob.delet.	N	0.459854573	None	None	N
K/P	0.7897	likely_pathogenic	0.8284	pathogenic	0.089	Stabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
K/Q	0.3573	ambiguous	0.3595	ambiguous	-0.201	Destabilizing	1.0	D	0.703	prob.neutral	N	0.473669232	None	None	N
K/R	0.1143	likely_benign	0.1202	benign	-0.173	Destabilizing	0.999	D	0.638	neutral	N	0.484118299	None	None	N
K/S	0.7777	likely_pathogenic	0.7678	pathogenic	-0.418	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	N
K/T	0.5185	ambiguous	0.503	ambiguous	-0.336	Destabilizing	1.0	D	0.674	neutral	N	0.468263412	None	None	N
K/V	0.6541	likely_pathogenic	0.6861	pathogenic	0.089	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
K/W	0.9385	likely_pathogenic	0.9477	pathogenic	-0.543	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
K/Y	0.9081	likely_pathogenic	0.908	pathogenic	-0.198	Destabilizing	1.0	D	0.712	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.