TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28689	86290;86291;86292	chr2:178560067;178560066;178560065	chr2:179424794;179424793;179424792
N2AB	27048	81367;81368;81369	chr2:178560067;178560066;178560065	chr2:179424794;179424793;179424792
N2A	26121	78586;78587;78588	chr2:178560067;178560066;178560065	chr2:179424794;179424793;179424792
N2B	19624	59095;59096;59097	chr2:178560067;178560066;178560065	chr2:179424794;179424793;179424792
Novex-1	19749	59470;59471;59472	chr2:178560067;178560066;178560065	chr2:179424794;179424793;179424792
Novex-2	19816	59671;59672;59673	chr2:178560067;178560066;178560065	chr2:179424794;179424793;179424792
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: Fn3-97
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.152
• 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	0.767	N	0.393	0.358	0.305730143919	gnomAD-4.0.0	4.80131E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25003E-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	0.4661	ambiguous	0.4746	ambiguous	-1.794	Destabilizing	0.996	D	0.631	neutral	N	0.512807988	None	None	N
E/C	0.9405	likely_pathogenic	0.9313	pathogenic	-1.015	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/D	0.5745	likely_pathogenic	0.5926	pathogenic	-1.658	Destabilizing	0.998	D	0.625	neutral	N	0.477840472	None	None	N
E/F	0.9621	likely_pathogenic	0.9599	pathogenic	-1.432	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/G	0.7107	likely_pathogenic	0.7106	pathogenic	-2.189	Highly Destabilizing	0.999	D	0.731	prob.delet.	N	0.519355355	None	None	N
E/H	0.8866	likely_pathogenic	0.8843	pathogenic	-1.366	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/I	0.7604	likely_pathogenic	0.7658	pathogenic	-0.654	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/K	0.777	likely_pathogenic	0.7797	pathogenic	-1.751	Destabilizing	0.767	D	0.393	neutral	N	0.502323829	None	None	N
E/L	0.8532	likely_pathogenic	0.8462	pathogenic	-0.654	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/M	0.7443	likely_pathogenic	0.7434	pathogenic	0.103	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/N	0.8443	likely_pathogenic	0.8452	pathogenic	-1.915	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/P	0.9991	likely_pathogenic	0.9989	pathogenic	-1.021	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/Q	0.2895	likely_benign	0.287	benign	-1.646	Destabilizing	0.996	D	0.7	prob.neutral	N	0.497412883	None	None	N
E/R	0.8401	likely_pathogenic	0.8326	pathogenic	-1.513	Destabilizing	0.998	D	0.762	deleterious	None	None	None	None	N
E/S	0.5736	likely_pathogenic	0.5793	pathogenic	-2.617	Highly Destabilizing	0.997	D	0.649	neutral	None	None	None	None	N
E/T	0.6686	likely_pathogenic	0.6656	pathogenic	-2.246	Highly Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/V	0.6065	likely_pathogenic	0.6134	pathogenic	-1.021	Destabilizing	0.999	D	0.753	deleterious	N	0.489703757	None	None	N
E/W	0.9879	likely_pathogenic	0.9861	pathogenic	-1.442	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
E/Y	0.949	likely_pathogenic	0.9436	pathogenic	-1.24	Destabilizing	1.0	D	0.813	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.