TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5537	16834;16835;16836	chr2:178732452;178732451;178732450	chr2:179597179;179597178;179597177
N2AB	5220	15883;15884;15885	chr2:178732452;178732451;178732450	chr2:179597179;179597178;179597177
N2A	4293	13102;13103;13104	chr2:178732452;178732451;178732450	chr2:179597179;179597178;179597177
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: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-38
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.1236
• 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
L/F	rs763076529	-1.727	0.997	N	0.831	0.449	0.494838880905	gnomAD-4.0.0	1.62702E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.92502E-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
L/A	0.8493	likely_pathogenic	0.8723	pathogenic	-2.885	Highly Destabilizing	0.966	D	0.691	prob.neutral	None	None	None	None	N
L/C	0.8138	likely_pathogenic	0.8309	pathogenic	-2.549	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/D	0.9972	likely_pathogenic	0.9978	pathogenic	-3.114	Highly Destabilizing	0.999	D	0.901	deleterious	None	None	None	None	N
L/E	0.9881	likely_pathogenic	0.9908	pathogenic	-2.842	Highly Destabilizing	0.998	D	0.893	deleterious	None	None	None	None	N
L/F	0.4615	ambiguous	0.5667	pathogenic	-1.834	Destabilizing	0.997	D	0.831	deleterious	N	0.513882215	None	None	N
L/G	0.9739	likely_pathogenic	0.9789	pathogenic	-3.485	Highly Destabilizing	0.998	D	0.901	deleterious	None	None	None	None	N
L/H	0.9568	likely_pathogenic	0.9658	pathogenic	-2.959	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/I	0.0842	likely_benign	0.0936	benign	-1.123	Destabilizing	0.966	D	0.627	neutral	None	None	None	None	N
L/K	0.9865	likely_pathogenic	0.9888	pathogenic	-2.261	Highly Destabilizing	0.998	D	0.892	deleterious	None	None	None	None	N
L/M	0.2979	likely_benign	0.344	ambiguous	-1.298	Destabilizing	0.997	D	0.803	deleterious	D	0.532493449	None	None	N
L/N	0.9812	likely_pathogenic	0.9833	pathogenic	-2.751	Highly Destabilizing	0.999	D	0.892	deleterious	None	None	None	None	N
L/P	0.9877	likely_pathogenic	0.9895	pathogenic	-1.695	Destabilizing	0.999	D	0.895	deleterious	None	None	None	None	N
L/Q	0.9593	likely_pathogenic	0.9664	pathogenic	-2.524	Highly Destabilizing	0.999	D	0.897	deleterious	None	None	None	None	N
L/R	0.9581	likely_pathogenic	0.9651	pathogenic	-2.067	Highly Destabilizing	0.999	D	0.904	deleterious	None	None	None	None	N
L/S	0.965	likely_pathogenic	0.9714	pathogenic	-3.526	Highly Destabilizing	0.997	D	0.887	deleterious	D	0.551358172	None	None	N
L/T	0.8454	likely_pathogenic	0.8709	pathogenic	-3.084	Highly Destabilizing	0.995	D	0.823	deleterious	None	None	None	None	N
L/V	0.0878	likely_benign	0.0963	benign	-1.695	Destabilizing	0.117	N	0.372	neutral	N	0.471612729	None	None	N
L/W	0.9106	likely_pathogenic	0.934	pathogenic	-2.17	Highly Destabilizing	1.0	D	0.86	deleterious	D	0.551358172	None	None	N
L/Y	0.8912	likely_pathogenic	0.9178	pathogenic	-1.935	Destabilizing	0.999	D	0.851	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.