TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5103	15532;15533;15534	chr2:178734517;178734516;178734515	chr2:179599244;179599243;179599242
N2AB	4786	14581;14582;14583	chr2:178734517;178734516;178734515	chr2:179599244;179599243;179599242
N2A	3859	11800;11801;11802	chr2:178734517;178734516;178734515	chr2:179599244;179599243;179599242
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: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-34
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.8692
• Predicted PPI site: I

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
P/L	None	None	1.0	D	0.694	0.507	0.82247249236	gnomAD-4.0.0	1.59216E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85987E-06	0	0
P/T	None	None	1.0	D	0.677	0.461	0.60416271137	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-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
P/A	0.2618	likely_benign	0.3075	benign	-0.385	Destabilizing	1.0	D	0.671	neutral	D	0.577567415	None	None	I
P/C	0.8544	likely_pathogenic	0.8904	pathogenic	-0.594	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
P/D	0.7621	likely_pathogenic	0.7847	pathogenic	-0.221	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
P/E	0.671	likely_pathogenic	0.7024	pathogenic	-0.323	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	I
P/F	0.8254	likely_pathogenic	0.8661	pathogenic	-0.599	Destabilizing	1.0	D	0.634	neutral	None	None	None	None	I
P/G	0.6563	likely_pathogenic	0.7065	pathogenic	-0.505	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
P/H	0.5323	ambiguous	0.5704	pathogenic	-0.053	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	I
P/I	0.6125	likely_pathogenic	0.6867	pathogenic	-0.213	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
P/K	0.7075	likely_pathogenic	0.7551	pathogenic	-0.378	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
P/L	0.3409	ambiguous	0.3892	ambiguous	-0.213	Destabilizing	1.0	D	0.694	prob.neutral	D	0.609220365	None	None	I
P/M	0.6587	likely_pathogenic	0.717	pathogenic	-0.441	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
P/N	0.6157	likely_pathogenic	0.6494	pathogenic	-0.127	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
P/Q	0.4728	ambiguous	0.5308	ambiguous	-0.335	Destabilizing	1.0	D	0.647	neutral	D	0.53713661	None	None	I
P/R	0.5349	ambiguous	0.5847	pathogenic	0.085	Stabilizing	1.0	D	0.677	prob.neutral	D	0.575633039	None	None	I
P/S	0.3906	ambiguous	0.4255	ambiguous	-0.467	Destabilizing	1.0	D	0.682	prob.neutral	D	0.579482874	None	None	I
P/T	0.3311	likely_benign	0.3723	ambiguous	-0.47	Destabilizing	1.0	D	0.677	prob.neutral	D	0.554460262	None	None	I
P/V	0.4955	ambiguous	0.5687	pathogenic	-0.238	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
P/W	0.9389	likely_pathogenic	0.9522	pathogenic	-0.687	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
P/Y	0.8132	likely_pathogenic	0.8461	pathogenic	-0.392	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	I

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.