TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10144	30655;30656;30657	chr2:178702457;178702456;178702455	chr2:179567184;179567183;179567182
N2AB	9827	29704;29705;29706	chr2:178702457;178702456;178702455	chr2:179567184;179567183;179567182
N2A	8900	26923;26924;26925	chr2:178702457;178702456;178702455	chr2:179567184;179567183;179567182
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-86
• Domain position: 67
• Structural Position: 151
• Q(SASA): 0.2436
• 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	None	None	0.999	None	0.581	0.377	0.478527412683	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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	0.7431	likely_pathogenic	0.7773	pathogenic	-0.731	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
E/C	0.995	likely_pathogenic	0.996	pathogenic	-0.349	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
E/D	0.9755	likely_pathogenic	0.9851	pathogenic	-1.034	Destabilizing	0.999	D	0.473	neutral	None	None	None	None	N
E/F	0.9985	likely_pathogenic	0.9989	pathogenic	0.024	Stabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
E/G	0.9051	likely_pathogenic	0.9339	pathogenic	-1.126	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/H	0.9937	likely_pathogenic	0.9959	pathogenic	-0.142	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/I	0.9692	likely_pathogenic	0.9768	pathogenic	0.353	Stabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
E/K	0.8741	likely_pathogenic	0.9081	pathogenic	-0.395	Destabilizing	0.999	D	0.581	neutral	None	None	None	None	N
E/L	0.9872	likely_pathogenic	0.9907	pathogenic	0.353	Stabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
E/M	0.9698	likely_pathogenic	0.9752	pathogenic	0.748	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/N	0.9854	likely_pathogenic	0.9911	pathogenic	-1.061	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/P	0.9991	likely_pathogenic	0.9991	pathogenic	0.013	Stabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
E/Q	0.6923	likely_pathogenic	0.7427	pathogenic	-0.876	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	N
E/R	0.9285	likely_pathogenic	0.9408	pathogenic	-0.07	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/S	0.9093	likely_pathogenic	0.9354	pathogenic	-1.351	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
E/T	0.9166	likely_pathogenic	0.934	pathogenic	-1.011	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
E/V	0.9275	likely_pathogenic	0.9431	pathogenic	0.013	Stabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
E/W	0.9995	likely_pathogenic	0.9997	pathogenic	0.324	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/Y	0.9974	likely_pathogenic	0.9982	pathogenic	0.305	Stabilizing	1.0	D	0.841	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.