TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14164	42715;42716;42717	chr2:178634009;178634008;178634007	chr2:179498736;179498735;179498734
N2AB	12523	37792;37793;37794	chr2:178634009;178634008;178634007	chr2:179498736;179498735;179498734
N2A	11596	35011;35012;35013	chr2:178634009;178634008;178634007	chr2:179498736;179498735;179498734
N2B	5099	15520;15521;15522	chr2:178634009;178634008;178634007	chr2:179498736;179498735;179498734
Novex-1	5224	15895;15896;15897	chr2:178634009;178634008;178634007	chr2:179498736;179498735;179498734
Novex-2	5291	16096;16097;16098	chr2:178634009;178634008;178634007	chr2:179498736;179498735;179498734
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-92
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.4546
• 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	rs1211763723	None	0.998	D	0.489	0.38	0.455081427078	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	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	0.2346	likely_benign	0.2543	benign	-0.783	Destabilizing	0.989	D	0.581	neutral	D	0.604427349	None	None	N
E/C	0.8581	likely_pathogenic	0.9002	pathogenic	-0.484	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/D	0.3008	likely_benign	0.3646	ambiguous	-1.303	Destabilizing	0.998	D	0.409	neutral	D	0.634868425	None	None	N
E/F	0.8122	likely_pathogenic	0.8571	pathogenic	-0.857	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
E/G	0.332	likely_benign	0.3737	ambiguous	-1.116	Destabilizing	0.999	D	0.705	prob.neutral	D	0.606858467	None	None	N
E/H	0.4777	ambiguous	0.5721	pathogenic	-1.199	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
E/I	0.3981	ambiguous	0.4547	ambiguous	0.115	Stabilizing	0.995	D	0.724	prob.delet.	None	None	None	None	N
E/K	0.1601	likely_benign	0.1921	benign	-0.773	Destabilizing	0.998	D	0.489	neutral	D	0.534421295	None	None	N
E/L	0.5018	ambiguous	0.5594	ambiguous	0.115	Stabilizing	0.983	D	0.688	prob.neutral	None	None	None	None	N
E/M	0.5214	ambiguous	0.5711	pathogenic	0.658	Stabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
E/N	0.3651	ambiguous	0.4352	ambiguous	-1.047	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/P	0.9393	likely_pathogenic	0.9622	pathogenic	-0.163	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/Q	0.122	likely_benign	0.1419	benign	-0.929	Destabilizing	0.999	D	0.603	neutral	D	0.582517232	None	None	N
E/R	0.2694	likely_benign	0.3335	benign	-0.72	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/S	0.2467	likely_benign	0.2947	benign	-1.432	Destabilizing	0.996	D	0.555	neutral	None	None	None	None	N
E/T	0.2108	likely_benign	0.2636	benign	-1.149	Destabilizing	0.998	D	0.724	prob.delet.	None	None	None	None	N
E/V	0.2396	likely_benign	0.279	benign	-0.163	Destabilizing	0.733	D	0.488	neutral	D	0.549617585	None	None	N
E/W	0.9477	likely_pathogenic	0.9647	pathogenic	-0.883	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
E/Y	0.739	likely_pathogenic	0.8025	pathogenic	-0.663	Destabilizing	1.0	D	0.775	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.