TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26749	80470;80471;80472	chr2:178565887;178565886;178565885	chr2:179430614;179430613;179430612
N2AB	25108	75547;75548;75549	chr2:178565887;178565886;178565885	chr2:179430614;179430613;179430612
N2A	24181	72766;72767;72768	chr2:178565887;178565886;178565885	chr2:179430614;179430613;179430612
N2B	17684	53275;53276;53277	chr2:178565887;178565886;178565885	chr2:179430614;179430613;179430612
Novex-1	17809	53650;53651;53652	chr2:178565887;178565886;178565885	chr2:179430614;179430613;179430612
Novex-2	17876	53851;53852;53853	chr2:178565887;178565886;178565885	chr2:179430614;179430613;179430612
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: Fn3-82
• Domain position: 67
• Structural Position: 99
• Q(SASA): 0.6146
• 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	None	None	0.997	N	0.703	0.439	0.403469152278	gnomAD-4.0.0	1.36854E-06	None	None	None	None	N	None	2.98864E-05	2.23634E-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	0.2996	likely_benign	0.2486	benign	-0.263	Destabilizing	0.995	D	0.657	neutral	N	0.469594358	None	None	N
E/C	0.9654	likely_pathogenic	0.9591	pathogenic	0.172	Stabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
E/D	0.5385	ambiguous	0.5039	ambiguous	-0.318	Destabilizing	0.965	D	0.594	neutral	N	0.511820483	None	None	N
E/F	0.9844	likely_pathogenic	0.9736	pathogenic	-0.334	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
E/G	0.5728	likely_pathogenic	0.4733	ambiguous	-0.439	Destabilizing	1.0	D	0.611	neutral	N	0.498742658	None	None	N
E/H	0.9149	likely_pathogenic	0.8859	pathogenic	-0.171	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	N
E/I	0.7644	likely_pathogenic	0.7308	pathogenic	0.155	Stabilizing	0.999	D	0.639	neutral	None	None	None	None	N
E/K	0.4864	ambiguous	0.425	ambiguous	0.452	Stabilizing	0.997	D	0.703	prob.neutral	N	0.49270227	None	None	N
E/L	0.8727	likely_pathogenic	0.8337	pathogenic	0.155	Stabilizing	0.999	D	0.633	neutral	None	None	None	None	N
E/M	0.8549	likely_pathogenic	0.8113	pathogenic	0.306	Stabilizing	0.998	D	0.597	neutral	None	None	None	None	N
E/N	0.7426	likely_pathogenic	0.7155	pathogenic	0.263	Stabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	N
E/P	0.6026	likely_pathogenic	0.631	pathogenic	0.036	Stabilizing	0.992	D	0.618	neutral	None	None	None	None	N
E/Q	0.3463	ambiguous	0.3118	benign	0.263	Stabilizing	0.999	D	0.689	prob.neutral	N	0.479624445	None	None	N
E/R	0.6863	likely_pathogenic	0.6251	pathogenic	0.554	Stabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
E/S	0.5142	ambiguous	0.4536	ambiguous	0.096	Stabilizing	0.997	D	0.702	prob.neutral	None	None	None	None	N
E/T	0.6099	likely_pathogenic	0.5533	ambiguous	0.234	Stabilizing	0.999	D	0.647	neutral	None	None	None	None	N
E/V	0.5323	ambiguous	0.489	ambiguous	0.036	Stabilizing	0.998	D	0.614	neutral	N	0.492399555	None	None	N
E/W	0.9954	likely_pathogenic	0.9926	pathogenic	-0.252	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
E/Y	0.97	likely_pathogenic	0.9527	pathogenic	-0.097	Destabilizing	1.0	D	0.605	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.