TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15072	45439;45440;45441	chr2:178621610;178621609;178621608	chr2:179486337;179486336;179486335
N2AB	13431	40516;40517;40518	chr2:178621610;178621609;178621608	chr2:179486337;179486336;179486335
N2A	12504	37735;37736;37737	chr2:178621610;178621609;178621608	chr2:179486337;179486336;179486335
N2B	6007	18244;18245;18246	chr2:178621610;178621609;178621608	chr2:179486337;179486336;179486335
Novex-1	6132	18619;18620;18621	chr2:178621610;178621609;178621608	chr2:179486337;179486336;179486335
Novex-2	6199	18820;18821;18822	chr2:178621610;178621609;178621608	chr2:179486337;179486336;179486335
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-102
• Domain position: 42
• Structural Position: 70
• Q(SASA): 0.5217
• 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
E/K	rs963923376	0.568	0.939	N	0.505	0.366	0.426551566703	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.95E-06	0
E/K	rs963923376	0.568	0.939	N	0.505	0.366	0.426551566703	gnomAD-4.0.0	2.73863E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99905E-07	2.31932E-05	1.65837E-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
E/A	0.158	likely_benign	0.171	benign	-0.327	Destabilizing	0.939	D	0.525	neutral	N	0.478445226	None	None	N
E/C	0.8955	likely_pathogenic	0.9157	pathogenic	-0.094	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	N
E/D	0.1925	likely_benign	0.2006	benign	-0.425	Destabilizing	0.02	N	0.22	neutral	N	0.446255996	None	None	N
E/F	0.8565	likely_pathogenic	0.8647	pathogenic	-0.105	Destabilizing	0.999	D	0.588	neutral	None	None	None	None	N
E/G	0.1574	likely_benign	0.1607	benign	-0.537	Destabilizing	0.939	D	0.462	neutral	N	0.511406037	None	None	N
E/H	0.5861	likely_pathogenic	0.5976	pathogenic	0.183	Stabilizing	0.999	D	0.533	neutral	None	None	None	None	N
E/I	0.5537	ambiguous	0.5486	ambiguous	0.195	Stabilizing	0.993	D	0.617	neutral	None	None	None	None	N
E/K	0.1712	likely_benign	0.1629	benign	0.421	Stabilizing	0.939	D	0.505	neutral	N	0.51191043	None	None	N
E/L	0.563	ambiguous	0.5704	pathogenic	0.195	Stabilizing	0.993	D	0.609	neutral	None	None	None	None	N
E/M	0.6205	likely_pathogenic	0.6276	pathogenic	0.196	Stabilizing	0.999	D	0.53	neutral	None	None	None	None	N
E/N	0.3371	likely_benign	0.3545	ambiguous	-0.087	Destabilizing	0.973	D	0.498	neutral	None	None	None	None	N
E/P	0.334	likely_benign	0.4055	ambiguous	0.041	Stabilizing	0.993	D	0.569	neutral	None	None	None	None	N
E/Q	0.1599	likely_benign	0.1625	benign	-0.021	Destabilizing	0.991	D	0.489	neutral	N	0.512264129	None	None	N
E/R	0.2832	likely_benign	0.2879	benign	0.645	Stabilizing	0.993	D	0.548	neutral	None	None	None	None	N
E/S	0.217	likely_benign	0.2402	benign	-0.19	Destabilizing	0.953	D	0.49	neutral	None	None	None	None	N
E/T	0.2887	likely_benign	0.2886	benign	-0.008	Destabilizing	0.986	D	0.518	neutral	None	None	None	None	N
E/V	0.3393	likely_benign	0.3397	benign	0.041	Stabilizing	0.991	D	0.545	neutral	N	0.516741885	None	None	N
E/W	0.9413	likely_pathogenic	0.9458	pathogenic	0.068	Stabilizing	0.999	D	0.629	neutral	None	None	None	None	N
E/Y	0.7457	likely_pathogenic	0.7607	pathogenic	0.149	Stabilizing	0.999	D	0.535	neutral	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.