TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24300	73123;73124;73125	chr2:178573234;178573233;178573232	chr2:179437961;179437960;179437959
N2AB	22659	68200;68201;68202	chr2:178573234;178573233;178573232	chr2:179437961;179437960;179437959
N2A	21732	65419;65420;65421	chr2:178573234;178573233;178573232	chr2:179437961;179437960;179437959
N2B	15235	45928;45929;45930	chr2:178573234;178573233;178573232	chr2:179437961;179437960;179437959
Novex-1	15360	46303;46304;46305	chr2:178573234;178573233;178573232	chr2:179437961;179437960;179437959
Novex-2	15427	46504;46505;46506	chr2:178573234;178573233;178573232	chr2:179437961;179437960;179437959
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: Fn3-64
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.1903
• 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	rs1222244205	-1.718	0.999	N	0.479	0.373	0.208000267992	gnomAD-2.1.1	4.1E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
E/D	rs1222244205	-1.718	0.999	N	0.479	0.373	0.208000267992	gnomAD-4.0.0	1.60856E-06	None	None	None	None	N	None	0	0	None	0	2.78319E-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	0.429	ambiguous	0.4142	ambiguous	-1.185	Destabilizing	0.999	D	0.654	neutral	N	0.472797135	None	None	N
E/C	0.9259	likely_pathogenic	0.9259	pathogenic	-0.726	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
E/D	0.7384	likely_pathogenic	0.7286	pathogenic	-1.523	Destabilizing	0.999	D	0.479	neutral	N	0.502968939	None	None	N
E/F	0.9404	likely_pathogenic	0.9397	pathogenic	-0.952	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
E/G	0.6012	likely_pathogenic	0.5597	ambiguous	-1.566	Destabilizing	1.0	D	0.745	deleterious	N	0.514325244	None	None	N
E/H	0.8748	likely_pathogenic	0.8716	pathogenic	-1.165	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
E/I	0.5598	ambiguous	0.5757	pathogenic	-0.129	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
E/K	0.3993	ambiguous	0.3775	ambiguous	-1.051	Destabilizing	0.999	D	0.509	neutral	N	0.474798598	None	None	N
E/L	0.7635	likely_pathogenic	0.7655	pathogenic	-0.129	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
E/M	0.6574	likely_pathogenic	0.667	pathogenic	0.494	Stabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
E/N	0.8002	likely_pathogenic	0.7788	pathogenic	-1.407	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
E/P	0.9972	likely_pathogenic	0.9975	pathogenic	-0.462	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/Q	0.2225	likely_benign	0.2155	benign	-1.249	Destabilizing	1.0	D	0.596	neutral	N	0.482102752	None	None	N
E/R	0.5992	likely_pathogenic	0.5824	pathogenic	-0.881	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/S	0.5845	likely_pathogenic	0.5544	ambiguous	-1.895	Destabilizing	0.999	D	0.532	neutral	None	None	None	None	N
E/T	0.6068	likely_pathogenic	0.57	pathogenic	-1.558	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/V	0.3501	ambiguous	0.3515	ambiguous	-0.462	Destabilizing	1.0	D	0.804	deleterious	N	0.434566552	None	None	N
E/W	0.9856	likely_pathogenic	0.9856	pathogenic	-0.863	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
E/Y	0.9247	likely_pathogenic	0.9251	pathogenic	-0.715	Destabilizing	1.0	D	0.845	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.