TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15840	47743;47744;47745	chr2:178617833;178617832;178617831	chr2:179482560;179482559;179482558
N2AB	14199	42820;42821;42822	chr2:178617833;178617832;178617831	chr2:179482560;179482559;179482558
N2A	13272	40039;40040;40041	chr2:178617833;178617832;178617831	chr2:179482560;179482559;179482558
N2B	6775	20548;20549;20550	chr2:178617833;178617832;178617831	chr2:179482560;179482559;179482558
Novex-1	6900	20923;20924;20925	chr2:178617833;178617832;178617831	chr2:179482560;179482559;179482558
Novex-2	6967	21124;21125;21126	chr2:178617833;178617832;178617831	chr2:179482560;179482559;179482558
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-2
• Domain position: 83
• Structural Position: 115
• Q(SASA): 0.1417
• 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
G/E	rs1406279657	-0.842	1.0	D	0.895	0.74	0.802058875851	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.66389E-04
G/E	rs1406279657	-0.842	1.0	D	0.895	0.74	0.802058875851	gnomAD-4.0.0	1.59399E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.03177E-05

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
G/A	0.836	likely_pathogenic	0.8288	pathogenic	-0.728	Destabilizing	1.0	D	0.747	deleterious	D	0.783453717	None	None	I
G/C	0.9533	likely_pathogenic	0.9478	pathogenic	-1.06	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
G/D	0.9627	likely_pathogenic	0.9681	pathogenic	-1.093	Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	I
G/E	0.9834	likely_pathogenic	0.9857	pathogenic	-1.221	Destabilizing	1.0	D	0.895	deleterious	D	0.783453717	None	None	I
G/F	0.9923	likely_pathogenic	0.993	pathogenic	-1.202	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
G/H	0.9891	likely_pathogenic	0.9884	pathogenic	-0.977	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
G/I	0.9903	likely_pathogenic	0.9918	pathogenic	-0.665	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
G/K	0.9889	likely_pathogenic	0.9887	pathogenic	-1.275	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	I
G/L	0.9847	likely_pathogenic	0.986	pathogenic	-0.665	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
G/M	0.9927	likely_pathogenic	0.9924	pathogenic	-0.577	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
G/N	0.9744	likely_pathogenic	0.9712	pathogenic	-0.945	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
G/P	0.9981	likely_pathogenic	0.9985	pathogenic	-0.65	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	I
G/Q	0.982	likely_pathogenic	0.9814	pathogenic	-1.243	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	I
G/R	0.9684	likely_pathogenic	0.9701	pathogenic	-0.751	Destabilizing	1.0	D	0.901	deleterious	D	0.78434732	None	None	I
G/S	0.7759	likely_pathogenic	0.7789	pathogenic	-1.128	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
G/T	0.9451	likely_pathogenic	0.9459	pathogenic	-1.193	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	I
G/V	0.9805	likely_pathogenic	0.9843	pathogenic	-0.65	Destabilizing	1.0	D	0.875	deleterious	D	0.728365637	None	None	I
G/W	0.9866	likely_pathogenic	0.9883	pathogenic	-1.375	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
G/Y	0.9884	likely_pathogenic	0.9892	pathogenic	-1.055	Destabilizing	1.0	D	0.879	deleterious	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.