TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22337	67234;67235;67236	chr2:178580370;178580369;178580368	chr2:179445097;179445096;179445095
N2AB	20696	62311;62312;62313	chr2:178580370;178580369;178580368	chr2:179445097;179445096;179445095
N2A	19769	59530;59531;59532	chr2:178580370;178580369;178580368	chr2:179445097;179445096;179445095
N2B	13272	40039;40040;40041	chr2:178580370;178580369;178580368	chr2:179445097;179445096;179445095
Novex-1	13397	40414;40415;40416	chr2:178580370;178580369;178580368	chr2:179445097;179445096;179445095
Novex-2	13464	40615;40616;40617	chr2:178580370;178580369;178580368	chr2:179445097;179445096;179445095
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-126
• Domain position: 73
• Structural Position: 159
• Q(SASA): 0.4694
• 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
E/K	rs764858373	0.093	0.944	D	0.612	0.387	0.420939154896	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	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	0.3824	ambiguous	0.3941	ambiguous	-0.68	Destabilizing	0.805	D	0.579	neutral	N	0.488530393	None	None	I
E/C	0.9194	likely_pathogenic	0.9199	pathogenic	-0.108	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	I
E/D	0.4246	ambiguous	0.4416	ambiguous	-0.78	Destabilizing	0.981	D	0.494	neutral	N	0.485429748	None	None	I
E/F	0.9343	likely_pathogenic	0.9372	pathogenic	-0.654	Destabilizing	0.975	D	0.751	deleterious	None	None	None	None	I
E/G	0.5573	ambiguous	0.5553	ambiguous	-0.935	Destabilizing	0.983	D	0.67	neutral	N	0.495571512	None	None	I
E/H	0.7335	likely_pathogenic	0.7307	pathogenic	-0.845	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	I
E/I	0.5961	likely_pathogenic	0.6237	pathogenic	-0.019	Destabilizing	0.95	D	0.703	prob.neutral	None	None	None	None	I
E/K	0.4259	ambiguous	0.4351	ambiguous	-0.054	Destabilizing	0.944	D	0.612	neutral	D	0.528189655	None	None	I
E/L	0.7593	likely_pathogenic	0.7695	pathogenic	-0.019	Destabilizing	0.845	D	0.695	prob.neutral	None	None	None	None	I
E/M	0.7103	likely_pathogenic	0.7153	pathogenic	0.372	Stabilizing	0.997	D	0.709	prob.delet.	None	None	None	None	I
E/N	0.6216	likely_pathogenic	0.6355	pathogenic	-0.34	Destabilizing	0.996	D	0.693	prob.neutral	None	None	None	None	I
E/P	0.996	likely_pathogenic	0.9961	pathogenic	-0.219	Destabilizing	0.996	D	0.709	prob.delet.	None	None	None	None	I
E/Q	0.203	likely_benign	0.2048	benign	-0.314	Destabilizing	0.994	D	0.637	neutral	N	0.511702837	None	None	I
E/R	0.5806	likely_pathogenic	0.5853	pathogenic	0.022	Stabilizing	0.987	D	0.688	prob.neutral	None	None	None	None	I
E/S	0.4138	ambiguous	0.4237	ambiguous	-0.557	Destabilizing	0.957	D	0.649	neutral	None	None	None	None	I
E/T	0.3876	ambiguous	0.4072	ambiguous	-0.352	Destabilizing	0.975	D	0.683	prob.neutral	None	None	None	None	I
E/V	0.3912	ambiguous	0.4103	ambiguous	-0.219	Destabilizing	0.056	N	0.465	neutral	N	0.490936703	None	None	I
E/W	0.9706	likely_pathogenic	0.9714	pathogenic	-0.513	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	I
E/Y	0.8829	likely_pathogenic	0.8882	pathogenic	-0.411	Destabilizing	0.987	D	0.724	prob.delet.	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.