TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5520	16783;16784;16785	chr2:178732503;178732502;178732501	chr2:179597230;179597229;179597228
N2AB	5203	15832;15833;15834	chr2:178732503;178732502;178732501	chr2:179597230;179597229;179597228
N2A	4276	13051;13052;13053	chr2:178732503;178732502;178732501	chr2:179597230;179597229;179597228
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-38
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1379
• 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
Y/C	None	None	1.0	D	0.848	0.714	0.86915730788	gnomAD-4.0.0	1.59156E-06	None	None	None	None	N	None	0	0	None	0	2.77469E-05	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
Y/A	0.9873	likely_pathogenic	0.9879	pathogenic	-2.585	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
Y/C	0.8729	likely_pathogenic	0.8775	pathogenic	-2.362	Highly Destabilizing	1.0	D	0.848	deleterious	D	0.655745042	None	None	N
Y/D	0.9968	likely_pathogenic	0.997	pathogenic	-2.577	Highly Destabilizing	1.0	D	0.877	deleterious	D	0.655745042	None	None	N
Y/E	0.9984	likely_pathogenic	0.9985	pathogenic	-2.344	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
Y/F	0.1667	likely_benign	0.1675	benign	-1.073	Destabilizing	0.999	D	0.679	prob.neutral	D	0.590608575	None	None	N
Y/G	0.9883	likely_pathogenic	0.9886	pathogenic	-3.037	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/H	0.9653	likely_pathogenic	0.9677	pathogenic	-2.107	Highly Destabilizing	1.0	D	0.775	deleterious	D	0.655543238	None	None	N
Y/I	0.7937	likely_pathogenic	0.8129	pathogenic	-1.103	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
Y/K	0.9982	likely_pathogenic	0.9983	pathogenic	-2.117	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
Y/L	0.7604	likely_pathogenic	0.7768	pathogenic	-1.103	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
Y/M	0.947	likely_pathogenic	0.9496	pathogenic	-1.321	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
Y/N	0.979	likely_pathogenic	0.9809	pathogenic	-2.907	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.655745042	None	None	N
Y/P	0.9972	likely_pathogenic	0.9973	pathogenic	-1.611	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/Q	0.9976	likely_pathogenic	0.9977	pathogenic	-2.516	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
Y/R	0.9917	likely_pathogenic	0.9919	pathogenic	-2.161	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
Y/S	0.9765	likely_pathogenic	0.9794	pathogenic	-3.418	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.655745042	None	None	N
Y/T	0.9878	likely_pathogenic	0.9888	pathogenic	-3.041	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
Y/V	0.6873	likely_pathogenic	0.7045	pathogenic	-1.611	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
Y/W	0.7417	likely_pathogenic	0.7544	pathogenic	-0.425	Destabilizing	1.0	D	0.768	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.