TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3202	9829;9830;9831	chr2:178766480;178766479;178766478	chr2:179631207;179631206;179631205
N2AB	3202	9829;9830;9831	chr2:178766480;178766479;178766478	chr2:179631207;179631206;179631205
N2A	3202	9829;9830;9831	chr2:178766480;178766479;178766478	chr2:179631207;179631206;179631205
N2B	3156	9691;9692;9693	chr2:178766480;178766479;178766478	chr2:179631207;179631206;179631205
Novex-1	3156	9691;9692;9693	chr2:178766480;178766479;178766478	chr2:179631207;179631206;179631205
Novex-2	3156	9691;9692;9693	chr2:178766480;178766479;178766478	chr2:179631207;179631206;179631205
Novex-3	3202	9829;9830;9831	chr2:178766480;178766479;178766478	chr2:179631207;179631206;179631205

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-22
• Domain position: 56
• Structural Position: 135
• Q(SASA): 0.3454
• 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/M	None	None	0.934	N	0.488	0.346	0.576839456108	gnomAD-4.0.0	1.59055E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85656E-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
I/A	0.9119	likely_pathogenic	0.889	pathogenic	-2.329	Highly Destabilizing	0.525	D	0.471	neutral	None	None	None	None	N
I/C	0.9397	likely_pathogenic	0.9243	pathogenic	-1.372	Destabilizing	0.998	D	0.507	neutral	None	None	None	None	N
I/D	0.9813	likely_pathogenic	0.9783	pathogenic	-2.608	Highly Destabilizing	0.991	D	0.639	neutral	None	None	None	None	N
I/E	0.9329	likely_pathogenic	0.9185	pathogenic	-2.536	Highly Destabilizing	0.974	D	0.621	neutral	None	None	None	None	N
I/F	0.45	ambiguous	0.467	ambiguous	-1.527	Destabilizing	0.934	D	0.457	neutral	N	0.49710086	None	None	N
I/G	0.971	likely_pathogenic	0.9673	pathogenic	-2.716	Highly Destabilizing	0.974	D	0.608	neutral	None	None	None	None	N
I/H	0.8529	likely_pathogenic	0.8475	pathogenic	-2.118	Highly Destabilizing	0.998	D	0.606	neutral	None	None	None	None	N
I/K	0.7775	likely_pathogenic	0.7562	pathogenic	-1.893	Destabilizing	0.974	D	0.614	neutral	None	None	None	None	N
I/L	0.2723	likely_benign	0.2688	benign	-1.266	Destabilizing	0.005	N	0.092	neutral	N	0.472097107	None	None	N
I/M	0.2813	likely_benign	0.2831	benign	-0.937	Destabilizing	0.934	D	0.488	neutral	N	0.506055392	None	None	N
I/N	0.7302	likely_pathogenic	0.73	pathogenic	-1.812	Destabilizing	0.989	D	0.647	neutral	N	0.50985534	None	None	N
I/P	0.9963	likely_pathogenic	0.9954	pathogenic	-1.597	Destabilizing	0.991	D	0.64	neutral	None	None	None	None	N
I/Q	0.8411	likely_pathogenic	0.8185	pathogenic	-1.927	Destabilizing	0.991	D	0.632	neutral	None	None	None	None	N
I/R	0.7132	likely_pathogenic	0.7033	pathogenic	-1.28	Destabilizing	0.991	D	0.647	neutral	None	None	None	None	N
I/S	0.838	likely_pathogenic	0.8243	pathogenic	-2.339	Highly Destabilizing	0.966	D	0.593	neutral	N	0.507914253	None	None	N
I/T	0.7282	likely_pathogenic	0.6733	pathogenic	-2.169	Highly Destabilizing	0.801	D	0.503	neutral	N	0.450821427	None	None	N
I/V	0.1688	likely_benign	0.1527	benign	-1.597	Destabilizing	0.002	N	0.114	neutral	N	0.422329814	None	None	N
I/W	0.9149	likely_pathogenic	0.9246	pathogenic	-1.808	Destabilizing	0.998	D	0.663	neutral	None	None	None	None	N
I/Y	0.765	likely_pathogenic	0.7685	pathogenic	-1.614	Destabilizing	0.991	D	0.545	neutral	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.