TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29018	87277;87278;87279	chr2:178558407;178558406;178558405	chr2:179423134;179423133;179423132
N2AB	27377	82354;82355;82356	chr2:178558407;178558406;178558405	chr2:179423134;179423133;179423132
N2A	26450	79573;79574;79575	chr2:178558407;178558406;178558405	chr2:179423134;179423133;179423132
N2B	19953	60082;60083;60084	chr2:178558407;178558406;178558405	chr2:179423134;179423133;179423132
Novex-1	20078	60457;60458;60459	chr2:178558407;178558406;178558405	chr2:179423134;179423133;179423132
Novex-2	20145	60658;60659;60660	chr2:178558407;178558406;178558405	chr2:179423134;179423133;179423132
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: Fn3-99
• Domain position: 77
• Structural Position: 111
• Q(SASA): 0.3165
• 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	None	None	0.992	N	0.469	0.365	0.286848849266	gnomAD-4.0.0	4.7898E-06	None	None	None	None	I	None	0	0	None	0	2.52538E-05	None	0	0	4.49729E-06	0	1.65678E-05

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	0.1738	likely_benign	0.1771	benign	-1.228	Destabilizing	0.996	D	0.593	neutral	N	0.499527682	None	None	I
E/C	0.8384	likely_pathogenic	0.8421	pathogenic	-0.842	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
E/D	0.5697	likely_pathogenic	0.5636	ambiguous	-1.648	Destabilizing	0.996	D	0.407	neutral	N	0.474002131	None	None	I
E/F	0.806	likely_pathogenic	0.8273	pathogenic	-1.014	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
E/G	0.2715	likely_benign	0.2658	benign	-1.633	Destabilizing	0.999	D	0.761	deleterious	N	0.480585496	None	None	I
E/H	0.5906	likely_pathogenic	0.634	pathogenic	-1.251	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
E/I	0.3599	ambiguous	0.3903	ambiguous	-0.094	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	I
E/K	0.1402	likely_benign	0.1544	benign	-1.353	Destabilizing	0.992	D	0.469	neutral	N	0.470861	None	None	I
E/L	0.4947	ambiguous	0.5199	ambiguous	-0.094	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
E/M	0.425	ambiguous	0.4399	ambiguous	0.569	Stabilizing	1.0	D	0.844	deleterious	None	None	None	None	I
E/N	0.6189	likely_pathogenic	0.602	pathogenic	-1.679	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
E/P	0.9873	likely_pathogenic	0.9905	pathogenic	-0.453	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
E/Q	0.1035	likely_benign	0.1067	benign	-1.437	Destabilizing	0.957	D	0.239	neutral	N	0.50212527	None	None	I
E/R	0.257	likely_benign	0.2926	benign	-1.206	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	I
E/S	0.2963	likely_benign	0.2866	benign	-2.23	Highly Destabilizing	0.997	D	0.557	neutral	None	None	None	None	I
E/T	0.3235	likely_benign	0.3355	benign	-1.866	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
E/V	0.1852	likely_benign	0.214	benign	-0.453	Destabilizing	0.999	D	0.826	deleterious	N	0.386890035	None	None	I
E/W	0.9369	likely_pathogenic	0.9497	pathogenic	-1.035	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
E/Y	0.7412	likely_pathogenic	0.7692	pathogenic	-0.824	Destabilizing	1.0	D	0.865	deleterious	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.