TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5613	17062;17063;17064	chr2:178732132;178732131;178732130	chr2:179596859;179596858;179596857
N2AB	5296	16111;16112;16113	chr2:178732132;178732131;178732130	chr2:179596859;179596858;179596857
N2A	4369	13330;13331;13332	chr2:178732132;178732131;178732130	chr2:179596859;179596858;179596857
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-39
• Domain position: 71
• Structural Position: 153
• Q(SASA): 0.6352
• 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/D	rs397517483	None	0.011	N	0.217	0.068	0.132336055621	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs397517483	None	0.011	N	0.217	0.068	0.132336055621	gnomAD-4.0.0	2.47881E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.54289E-06	0	1.60108E-05
E/Q	rs2080652790	None	0.98	N	0.583	0.267	0.319114376414	gnomAD-4.0.0	1.59143E-06	None	None	None	None	N	None	0	0	None	0	2.773E-05	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	0.2122	likely_benign	0.2244	benign	-0.583	Destabilizing	0.98	D	0.627	neutral	N	0.504083431	None	None	N
E/C	0.887	likely_pathogenic	0.9118	pathogenic	-0.11	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
E/D	0.1578	likely_benign	0.1677	benign	-0.968	Destabilizing	0.011	N	0.217	neutral	N	0.419312751	None	None	N
E/F	0.7188	likely_pathogenic	0.7445	pathogenic	-0.69	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	N
E/G	0.2637	likely_benign	0.2958	benign	-0.87	Destabilizing	0.961	D	0.627	neutral	N	0.496545791	None	None	N
E/H	0.5396	ambiguous	0.5668	pathogenic	-1.079	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
E/I	0.3341	likely_benign	0.3579	ambiguous	0.168	Stabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
E/K	0.2079	likely_benign	0.2093	benign	-0.209	Destabilizing	0.961	D	0.599	neutral	N	0.490767417	None	None	N
E/L	0.4384	ambiguous	0.4609	ambiguous	0.168	Stabilizing	0.996	D	0.716	prob.delet.	None	None	None	None	N
E/M	0.46	ambiguous	0.4856	ambiguous	0.681	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/N	0.2872	likely_benign	0.3015	benign	-0.506	Destabilizing	0.97	D	0.597	neutral	None	None	None	None	N
E/P	0.729	likely_pathogenic	0.7301	pathogenic	-0.061	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
E/Q	0.1751	likely_benign	0.1819	benign	-0.437	Destabilizing	0.98	D	0.583	neutral	N	0.489364695	None	None	N
E/R	0.3485	ambiguous	0.3531	ambiguous	-0.249	Destabilizing	0.996	D	0.629	neutral	None	None	None	None	N
E/S	0.2569	likely_benign	0.2767	benign	-0.756	Destabilizing	0.97	D	0.59	neutral	None	None	None	None	N
E/T	0.2614	likely_benign	0.2777	benign	-0.515	Destabilizing	0.985	D	0.639	neutral	None	None	None	None	N
E/V	0.2217	likely_benign	0.2352	benign	-0.061	Destabilizing	0.998	D	0.69	prob.neutral	N	0.449750301	None	None	N
E/W	0.9046	likely_pathogenic	0.916	pathogenic	-0.651	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/Y	0.6182	likely_pathogenic	0.6488	pathogenic	-0.471	Destabilizing	0.999	D	0.728	prob.delet.	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.