TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2231	6916;6917;6918	chr2:178775020;178775019;178775018	chr2:179639747;179639746;179639745
N2AB	2231	6916;6917;6918	chr2:178775020;178775019;178775018	chr2:179639747;179639746;179639745
N2A	2231	6916;6917;6918	chr2:178775020;178775019;178775018	chr2:179639747;179639746;179639745
N2B	2185	6778;6779;6780	chr2:178775020;178775019;178775018	chr2:179639747;179639746;179639745
Novex-1	2185	6778;6779;6780	chr2:178775020;178775019;178775018	chr2:179639747;179639746;179639745
Novex-2	2185	6778;6779;6780	chr2:178775020;178775019;178775018	chr2:179639747;179639746;179639745
Novex-3	2231	6916;6917;6918	chr2:178775020;178775019;178775018	chr2:179639747;179639746;179639745

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-11
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0564
• 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
L/F	None	None	0.142	D	0.471	0.36	0.370240404367	gnomAD-4.0.0	1.59083E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85691E-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
L/A	0.9441	likely_pathogenic	0.9354	pathogenic	-2.054	Highly Destabilizing	0.968	D	0.794	deleterious	None	None	None	None	N
L/C	0.8921	likely_pathogenic	0.879	pathogenic	-1.208	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9997	pathogenic	-2.791	Highly Destabilizing	0.998	D	0.937	deleterious	None	None	None	None	N
L/E	0.9976	likely_pathogenic	0.9972	pathogenic	-2.469	Highly Destabilizing	0.998	D	0.907	deleterious	None	None	None	None	N
L/F	0.503	ambiguous	0.5065	ambiguous	-1.263	Destabilizing	0.142	N	0.471	neutral	D	0.550236302	None	None	N
L/G	0.9909	likely_pathogenic	0.9892	pathogenic	-2.64	Highly Destabilizing	0.995	D	0.909	deleterious	None	None	None	None	N
L/H	0.9839	likely_pathogenic	0.9818	pathogenic	-2.653	Highly Destabilizing	0.999	D	0.932	deleterious	D	0.631295246	None	None	N
L/I	0.3179	likely_benign	0.3085	benign	-0.289	Destabilizing	0.919	D	0.716	prob.delet.	D	0.623982142	None	None	N
L/K	0.9937	likely_pathogenic	0.9931	pathogenic	-1.369	Destabilizing	0.995	D	0.909	deleterious	None	None	None	None	N
L/M	0.3367	likely_benign	0.3191	benign	-0.554	Destabilizing	0.995	D	0.799	deleterious	None	None	None	None	N
L/N	0.9968	likely_pathogenic	0.9962	pathogenic	-2.123	Highly Destabilizing	0.998	D	0.94	deleterious	None	None	None	None	N
L/P	0.9987	likely_pathogenic	0.9987	pathogenic	-0.869	Destabilizing	0.998	D	0.939	deleterious	D	0.631295246	None	None	N
L/Q	0.9766	likely_pathogenic	0.9724	pathogenic	-1.69	Destabilizing	1.0	D	0.935	deleterious	None	None	None	None	N
L/R	0.9842	likely_pathogenic	0.9828	pathogenic	-1.767	Destabilizing	0.994	D	0.918	deleterious	D	0.631295246	None	None	N
L/S	0.9904	likely_pathogenic	0.9886	pathogenic	-2.568	Highly Destabilizing	0.995	D	0.903	deleterious	None	None	None	None	N
L/T	0.9788	likely_pathogenic	0.9739	pathogenic	-2.074	Highly Destabilizing	0.995	D	0.837	deleterious	None	None	None	None	N
L/V	0.4154	ambiguous	0.4002	ambiguous	-0.869	Destabilizing	0.958	D	0.738	prob.delet.	D	0.54120758	None	None	N
L/W	0.9605	likely_pathogenic	0.9615	pathogenic	-1.638	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/Y	0.9642	likely_pathogenic	0.9629	pathogenic	-1.388	Destabilizing	0.982	D	0.851	deleterious	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.