TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26612	80059;80060;80061	chr2:178566298;178566297;178566296	chr2:179431025;179431024;179431023
N2AB	24971	75136;75137;75138	chr2:178566298;178566297;178566296	chr2:179431025;179431024;179431023
N2A	24044	72355;72356;72357	chr2:178566298;178566297;178566296	chr2:179431025;179431024;179431023
N2B	17547	52864;52865;52866	chr2:178566298;178566297;178566296	chr2:179431025;179431024;179431023
Novex-1	17672	53239;53240;53241	chr2:178566298;178566297;178566296	chr2:179431025;179431024;179431023
Novex-2	17739	53440;53441;53442	chr2:178566298;178566297;178566296	chr2:179431025;179431024;179431023
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-138
• Domain position: 19
• Structural Position: 30
• Q(SASA): 0.1731
• 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
I/V	None	None	0.426	N	0.448	0.227	0.596036732933	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	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
I/A	0.9811	likely_pathogenic	0.9776	pathogenic	-2.481	Highly Destabilizing	0.916	D	0.707	prob.neutral	None	None	None	None	N
I/C	0.9682	likely_pathogenic	0.9628	pathogenic	-1.801	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	N
I/D	0.9993	likely_pathogenic	0.9992	pathogenic	-2.783	Highly Destabilizing	0.996	D	0.827	deleterious	None	None	None	None	N
I/E	0.998	likely_pathogenic	0.9977	pathogenic	-2.522	Highly Destabilizing	0.987	D	0.827	deleterious	None	None	None	None	N
I/F	0.5089	ambiguous	0.4577	ambiguous	-1.52	Destabilizing	0.967	D	0.718	prob.delet.	N	0.478424478	None	None	N
I/G	0.9956	likely_pathogenic	0.9948	pathogenic	-3.019	Highly Destabilizing	0.987	D	0.829	deleterious	None	None	None	None	N
I/H	0.9951	likely_pathogenic	0.9941	pathogenic	-2.322	Highly Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
I/K	0.9946	likely_pathogenic	0.9941	pathogenic	-2.085	Highly Destabilizing	0.987	D	0.827	deleterious	None	None	None	None	N
I/L	0.2282	likely_benign	0.2271	benign	-0.909	Destabilizing	0.011	N	0.311	neutral	N	0.37377717	None	None	N
I/M	0.3273	likely_benign	0.3122	benign	-0.858	Destabilizing	0.967	D	0.684	prob.neutral	N	0.48137993	None	None	N
I/N	0.9893	likely_pathogenic	0.9874	pathogenic	-2.596	Highly Destabilizing	0.994	D	0.825	deleterious	N	0.52023268	None	None	N
I/P	0.997	likely_pathogenic	0.9969	pathogenic	-1.417	Destabilizing	0.996	D	0.822	deleterious	None	None	None	None	N
I/Q	0.9944	likely_pathogenic	0.9932	pathogenic	-2.374	Highly Destabilizing	0.996	D	0.825	deleterious	None	None	None	None	N
I/R	0.9927	likely_pathogenic	0.9917	pathogenic	-1.914	Destabilizing	0.987	D	0.819	deleterious	None	None	None	None	N
I/S	0.9892	likely_pathogenic	0.9871	pathogenic	-3.255	Highly Destabilizing	0.983	D	0.796	deleterious	N	0.52023268	None	None	N
I/T	0.9905	likely_pathogenic	0.988	pathogenic	-2.831	Highly Destabilizing	0.967	D	0.755	deleterious	N	0.51997919	None	None	N
I/V	0.2692	likely_benign	0.2479	benign	-1.417	Destabilizing	0.426	N	0.448	neutral	N	0.512356198	None	None	N
I/W	0.983	likely_pathogenic	0.9811	pathogenic	-1.807	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
I/Y	0.9406	likely_pathogenic	0.9359	pathogenic	-1.536	Destabilizing	0.987	D	0.722	prob.delet.	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.