TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14697	44314;44315;44316	chr2:178630869;178630868;178630867	chr2:179495596;179495595;179495594
N2AB	13056	39391;39392;39393	chr2:178630869;178630868;178630867	chr2:179495596;179495595;179495594
N2A	12129	36610;36611;36612	chr2:178630869;178630868;178630867	chr2:179495596;179495595;179495594
N2B	5632	17119;17120;17121	chr2:178630869;178630868;178630867	chr2:179495596;179495595;179495594
Novex-1	5757	17494;17495;17496	chr2:178630869;178630868;178630867	chr2:179495596;179495595;179495594
Novex-2	5824	17695;17696;17697	chr2:178630869;178630868;178630867	chr2:179495596;179495595;179495594
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-98
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.1969
• 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	rs1356852922	-1.113	1.0	D	0.669	0.375	0.248417906384	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	4.13E-05	0	None	0	0	None	3.27E-05	None	0	7.81E-06	0
E/K	rs1356852922	-1.113	1.0	D	0.669	0.375	0.248417906384	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs1356852922	-1.113	1.0	D	0.669	0.375	0.248417906384	gnomAD-4.0.0	1.41008E-05	None	None	None	None	N	None	8.46167E-05	0	None	0	0	None	0	0	7.18343E-06	4.02134E-05	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	0.3635	ambiguous	0.294	benign	-1.237	Destabilizing	0.997	D	0.759	deleterious	D	0.564367487	None	None	N
E/C	0.9682	likely_pathogenic	0.9531	pathogenic	-0.855	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
E/D	0.7113	likely_pathogenic	0.6651	pathogenic	-1.536	Destabilizing	0.997	D	0.652	prob.neutral	N	0.495161821	None	None	N
E/F	0.9455	likely_pathogenic	0.9269	pathogenic	-0.855	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
E/G	0.6532	likely_pathogenic	0.5362	ambiguous	-1.621	Destabilizing	0.999	D	0.781	deleterious	D	0.605096943	None	None	N
E/H	0.8849	likely_pathogenic	0.8362	pathogenic	-1.085	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/I	0.606	likely_pathogenic	0.5478	ambiguous	-0.164	Destabilizing	0.999	D	0.882	deleterious	None	None	None	None	N
E/K	0.4733	ambiguous	0.3517	ambiguous	-1.302	Destabilizing	1.0	D	0.669	prob.neutral	D	0.563148404	None	None	N
E/L	0.7983	likely_pathogenic	0.735	pathogenic	-0.164	Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	N
E/M	0.7054	likely_pathogenic	0.6332	pathogenic	0.397	Stabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
E/N	0.798	likely_pathogenic	0.7355	pathogenic	-1.573	Destabilizing	0.999	D	0.725	deleterious	None	None	None	None	N
E/P	0.9968	likely_pathogenic	0.9937	pathogenic	-0.503	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
E/Q	0.2712	likely_benign	0.2278	benign	-1.415	Destabilizing	1.0	D	0.641	neutral	D	0.525436174	None	None	N
E/R	0.6721	likely_pathogenic	0.5574	ambiguous	-1.055	Destabilizing	0.999	D	0.733	deleterious	None	None	None	None	N
E/S	0.5338	ambiguous	0.4632	ambiguous	-2.092	Highly Destabilizing	0.998	D	0.655	prob.neutral	None	None	None	None	N
E/T	0.5189	ambiguous	0.4402	ambiguous	-1.761	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
E/V	0.3706	ambiguous	0.3211	benign	-0.503	Destabilizing	0.999	D	0.838	deleterious	D	0.600667521	None	None	N
E/W	0.9883	likely_pathogenic	0.9829	pathogenic	-0.756	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
E/Y	0.9362	likely_pathogenic	0.9116	pathogenic	-0.634	Destabilizing	1.0	D	0.885	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.