TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29826	89701;89702;89703	chr2:178553529;178553528;178553527	chr2:179418256;179418255;179418254
N2AB	28185	84778;84779;84780	chr2:178553529;178553528;178553527	chr2:179418256;179418255;179418254
N2A	27258	81997;81998;81999	chr2:178553529;178553528;178553527	chr2:179418256;179418255;179418254
N2B	20761	62506;62507;62508	chr2:178553529;178553528;178553527	chr2:179418256;179418255;179418254
Novex-1	20886	62881;62882;62883	chr2:178553529;178553528;178553527	chr2:179418256;179418255;179418254
Novex-2	20953	63082;63083;63084	chr2:178553529;178553528;178553527	chr2:179418256;179418255;179418254
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: Fn3-105
• Domain position: 93
• Structural Position: 125
• Q(SASA): 0.6212
• 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/V	rs1345868585	0.313	0.993	N	0.507	0.356	0.527709697666	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
E/V	rs1345868585	0.313	0.993	N	0.507	0.356	0.527709697666	gnomAD-4.0.0	1.59277E-06	None	None	None	None	N	None	0	2.28896E-05	None	0	0	None	0	0	0	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
E/A	0.1545	likely_benign	0.1558	benign	-0.229	Destabilizing	0.953	D	0.503	neutral	N	0.502893274	None	None	N
E/C	0.7909	likely_pathogenic	0.7968	pathogenic	-0.353	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
E/D	0.1038	likely_benign	0.1114	benign	-0.204	Destabilizing	0.893	D	0.469	neutral	N	0.453235245	None	None	N
E/F	0.6835	likely_pathogenic	0.6849	pathogenic	-0.102	Destabilizing	0.998	D	0.776	deleterious	None	None	None	None	N
E/G	0.1645	likely_benign	0.1713	benign	-0.394	Destabilizing	0.976	D	0.516	neutral	N	0.485059661	None	None	N
E/H	0.4246	ambiguous	0.4443	ambiguous	0.464	Stabilizing	0.995	D	0.568	neutral	None	None	None	None	N
E/I	0.279	likely_benign	0.2835	benign	0.164	Stabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
E/K	0.1485	likely_benign	0.1433	benign	0.165	Stabilizing	0.91	D	0.519	neutral	N	0.496756735	None	None	N
E/L	0.3386	likely_benign	0.3397	benign	0.164	Stabilizing	0.99	D	0.539	neutral	None	None	None	None	N
E/M	0.4071	ambiguous	0.394	ambiguous	-0.076	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/N	0.2243	likely_benign	0.2368	benign	-0.059	Destabilizing	0.995	D	0.531	neutral	None	None	None	None	N
E/P	0.6587	likely_pathogenic	0.6497	pathogenic	0.051	Stabilizing	0.998	D	0.593	neutral	None	None	None	None	N
E/Q	0.1349	likely_benign	0.1361	benign	-0.024	Destabilizing	0.441	N	0.158	neutral	N	0.466665902	None	None	N
E/R	0.2703	likely_benign	0.2792	benign	0.529	Stabilizing	0.964	D	0.53	neutral	None	None	None	None	N
E/S	0.1754	likely_benign	0.19	benign	-0.266	Destabilizing	0.964	D	0.449	neutral	None	None	None	None	N
E/T	0.1644	likely_benign	0.1759	benign	-0.128	Destabilizing	0.982	D	0.565	neutral	None	None	None	None	N
E/V	0.1779	likely_benign	0.1782	benign	0.051	Stabilizing	0.993	D	0.507	neutral	N	0.517574725	None	None	N
E/W	0.8971	likely_pathogenic	0.8912	pathogenic	0.014	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/Y	0.5498	ambiguous	0.5495	ambiguous	0.13	Stabilizing	0.998	D	0.789	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.