TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8446	25561;25562;25563	chr2:178717538;178717537;178717536	chr2:179582265;179582264;179582263
N2AB	8129	24610;24611;24612	chr2:178717538;178717537;178717536	chr2:179582265;179582264;179582263
N2A	7202	21829;21830;21831	chr2:178717538;178717537;178717536	chr2:179582265;179582264;179582263
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-69
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.6994
• 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
K/E	None	None	0.996	N	0.565	0.255	0.30212335484	gnomAD-4.0.0	1.61293E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4579E-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
K/A	0.4708	ambiguous	0.4787	ambiguous	-0.634	Destabilizing	0.998	D	0.622	neutral	None	None	None	None	N
K/C	0.8199	likely_pathogenic	0.8107	pathogenic	-0.615	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
K/D	0.7299	likely_pathogenic	0.7409	pathogenic	-0.341	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
K/E	0.2629	likely_benign	0.2701	benign	-0.227	Destabilizing	0.996	D	0.565	neutral	N	0.461348588	None	None	N
K/F	0.8025	likely_pathogenic	0.8143	pathogenic	-0.275	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
K/G	0.6392	likely_pathogenic	0.6498	pathogenic	-1.015	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
K/H	0.3312	likely_benign	0.3253	benign	-1.354	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
K/I	0.4517	ambiguous	0.4674	ambiguous	0.36	Stabilizing	0.981	D	0.741	deleterious	None	None	None	None	N
K/L	0.4372	ambiguous	0.4396	ambiguous	0.36	Stabilizing	0.938	D	0.679	prob.neutral	None	None	None	None	N
K/M	0.3119	likely_benign	0.322	benign	0.295	Stabilizing	1.0	D	0.719	prob.delet.	N	0.520650394	None	None	N
K/N	0.5027	ambiguous	0.504	ambiguous	-0.606	Destabilizing	1.0	D	0.669	neutral	N	0.498253537	None	None	N
K/P	0.8708	likely_pathogenic	0.8587	pathogenic	0.059	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/Q	0.1594	likely_benign	0.1594	benign	-0.679	Destabilizing	0.999	D	0.701	prob.neutral	N	0.492423643	None	None	N
K/R	0.0811	likely_benign	0.0823	benign	-0.722	Destabilizing	0.993	D	0.55	neutral	N	0.464757039	None	None	N
K/S	0.4923	ambiguous	0.5007	ambiguous	-1.246	Destabilizing	0.996	D	0.564	neutral	None	None	None	None	N
K/T	0.2075	likely_benign	0.219	benign	-0.923	Destabilizing	0.608	D	0.42	neutral	N	0.473509808	None	None	N
K/V	0.4022	ambiguous	0.4126	ambiguous	0.059	Stabilizing	0.986	D	0.693	prob.neutral	None	None	None	None	N
K/W	0.7921	likely_pathogenic	0.7975	pathogenic	-0.151	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
K/Y	0.6597	likely_pathogenic	0.6755	pathogenic	0.129	Stabilizing	0.998	D	0.751	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.