TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33737	101434;101435;101436	chr2:178535406;178535405;178535404	chr2:179400133;179400132;179400131
N2AB	32096	96511;96512;96513	chr2:178535406;178535405;178535404	chr2:179400133;179400132;179400131
N2A	31169	93730;93731;93732	chr2:178535406;178535405;178535404	chr2:179400133;179400132;179400131
N2B	24672	74239;74240;74241	chr2:178535406;178535405;178535404	chr2:179400133;179400132;179400131
Novex-1	24797	74614;74615;74616	chr2:178535406;178535405;178535404	chr2:179400133;179400132;179400131
Novex-2	24864	74815;74816;74817	chr2:178535406;178535405;178535404	chr2:179400133;179400132;179400131
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-132
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.4272
• 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
L/F	rs1690979679	None	0.37	N	0.51	0.145	0.156986980423	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
L/A	0.5716	likely_pathogenic	0.482	ambiguous	-1.318	Destabilizing	0.218	N	0.519	neutral	None	None	None	None	I
L/C	0.7827	likely_pathogenic	0.7169	pathogenic	-0.681	Destabilizing	0.978	D	0.584	neutral	None	None	None	None	I
L/D	0.9438	likely_pathogenic	0.9031	pathogenic	-0.787	Destabilizing	0.798	D	0.632	neutral	None	None	None	None	I
L/E	0.6886	likely_pathogenic	0.5529	ambiguous	-0.81	Destabilizing	0.745	D	0.641	neutral	None	None	None	None	I
L/F	0.3828	ambiguous	0.285	benign	-0.924	Destabilizing	0.37	N	0.51	neutral	N	0.415701151	None	None	I
L/G	0.8419	likely_pathogenic	0.796	pathogenic	-1.594	Destabilizing	0.798	D	0.639	neutral	None	None	None	None	I
L/H	0.6139	likely_pathogenic	0.485	ambiguous	-0.762	Destabilizing	0.934	D	0.667	neutral	N	0.434209554	None	None	I
L/I	0.0679	likely_benign	0.0641	benign	-0.658	Destabilizing	None	N	0.12	neutral	N	0.387802473	None	None	I
L/K	0.6534	likely_pathogenic	0.5202	ambiguous	-0.882	Destabilizing	0.104	N	0.612	neutral	None	None	None	None	I
L/M	0.1265	likely_benign	0.1169	benign	-0.521	Destabilizing	0.189	N	0.53	neutral	None	None	None	None	I
L/N	0.57	likely_pathogenic	0.4791	ambiguous	-0.674	Destabilizing	0.923	D	0.641	neutral	None	None	None	None	I
L/P	0.9719	likely_pathogenic	0.969	pathogenic	-0.846	Destabilizing	0.901	D	0.64	neutral	N	0.488158682	None	None	I
L/Q	0.3484	ambiguous	0.2481	benign	-0.872	Destabilizing	0.833	D	0.607	neutral	None	None	None	None	I
L/R	0.628	likely_pathogenic	0.5002	ambiguous	-0.256	Destabilizing	0.543	D	0.607	neutral	N	0.411967412	None	None	I
L/S	0.6681	likely_pathogenic	0.5598	ambiguous	-1.204	Destabilizing	0.798	D	0.562	neutral	None	None	None	None	I
L/T	0.4666	ambiguous	0.3623	ambiguous	-1.12	Destabilizing	0.143	N	0.493	neutral	None	None	None	None	I
L/V	0.1271	likely_benign	0.1057	benign	-0.846	Destabilizing	None	N	0.152	neutral	N	0.378758916	None	None	I
L/W	0.7061	likely_pathogenic	0.6068	pathogenic	-0.984	Destabilizing	0.985	D	0.681	prob.neutral	None	None	None	None	I
L/Y	0.698	likely_pathogenic	0.594	pathogenic	-0.765	Destabilizing	0.156	N	0.55	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.