TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5508	16747;16748;16749	chr2:178732539;178732538;178732537	chr2:179597266;179597265;179597264
N2AB	5191	15796;15797;15798	chr2:178732539;178732538;178732537	chr2:179597266;179597265;179597264
N2A	4264	13015;13016;13017	chr2:178732539;178732538;178732537	chr2:179597266;179597265;179597264
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-38
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.4036
• 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/G	None	None	0.999	N	0.721	0.538	0.60906947716	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	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
E/A	0.2454	likely_benign	0.2778	benign	-0.782	Destabilizing	0.996	D	0.613	neutral	N	0.493112296	None	None	N
E/C	0.8529	likely_pathogenic	0.8715	pathogenic	-0.473	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/D	0.2921	likely_benign	0.3382	benign	-1.453	Destabilizing	0.996	D	0.529	neutral	N	0.494379744	None	None	N
E/F	0.7606	likely_pathogenic	0.7989	pathogenic	-0.192	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/G	0.3662	ambiguous	0.4255	ambiguous	-1.24	Destabilizing	0.999	D	0.721	prob.delet.	N	0.500963109	None	None	N
E/H	0.4821	ambiguous	0.5289	ambiguous	-0.602	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/I	0.3937	ambiguous	0.4381	ambiguous	0.501	Stabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
E/K	0.2479	likely_benign	0.3162	benign	-0.91	Destabilizing	0.992	D	0.569	neutral	N	0.518108734	None	None	N
E/L	0.4653	ambiguous	0.5177	ambiguous	0.501	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/M	0.4864	ambiguous	0.532	ambiguous	1.123	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/N	0.4024	ambiguous	0.4678	ambiguous	-1.428	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/P	0.9725	likely_pathogenic	0.9808	pathogenic	0.095	Stabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/Q	0.1334	likely_benign	0.1478	benign	-1.146	Destabilizing	0.957	D	0.356	neutral	N	0.515665862	None	None	N
E/R	0.3491	ambiguous	0.4114	ambiguous	-0.786	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
E/S	0.3055	likely_benign	0.3518	ambiguous	-1.924	Destabilizing	0.997	D	0.607	neutral	None	None	None	None	N
E/T	0.2839	likely_benign	0.3223	benign	-1.514	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
E/V	0.2333	likely_benign	0.2606	benign	0.095	Stabilizing	0.999	D	0.76	deleterious	N	0.478704984	None	None	N
E/W	0.9147	likely_pathogenic	0.93	pathogenic	-0.108	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/Y	0.6489	likely_pathogenic	0.6962	pathogenic	0.04	Stabilizing	1.0	D	0.784	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.