TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35012	105259;105260;105261	chr2:178531581;178531580;178531579	chr2:179396308;179396307;179396306
N2AB	33371	100336;100337;100338	chr2:178531581;178531580;178531579	chr2:179396308;179396307;179396306
N2A	32444	97555;97556;97557	chr2:178531581;178531580;178531579	chr2:179396308;179396307;179396306
N2B	25947	78064;78065;78066	chr2:178531581;178531580;178531579	chr2:179396308;179396307;179396306
Novex-1	26072	78439;78440;78441	chr2:178531581;178531580;178531579	chr2:179396308;179396307;179396306
Novex-2	26139	78640;78641;78642	chr2:178531581;178531580;178531579	chr2:179396308;179396307;179396306
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-163
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.0967
• 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/H	None	None	1.0	D	0.79	0.897	0.714837780597	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
Y/A	0.9987	likely_pathogenic	0.9989	pathogenic	-2.528	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/C	0.9755	likely_pathogenic	0.9801	pathogenic	-1.865	Destabilizing	1.0	D	0.846	deleterious	D	0.629510437	None	None	N
Y/D	0.9992	likely_pathogenic	0.9993	pathogenic	-3.404	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.629510437	None	None	N
Y/E	0.9996	likely_pathogenic	0.9997	pathogenic	-3.17	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/F	0.2914	likely_benign	0.3468	ambiguous	-0.872	Destabilizing	0.999	D	0.7	prob.neutral	D	0.595019703	None	None	N
Y/G	0.9973	likely_pathogenic	0.9975	pathogenic	-2.969	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/H	0.9935	likely_pathogenic	0.9951	pathogenic	-2.178	Highly Destabilizing	1.0	D	0.79	deleterious	D	0.629308632	None	None	N
Y/I	0.959	likely_pathogenic	0.9661	pathogenic	-1.055	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/K	0.9996	likely_pathogenic	0.9997	pathogenic	-2.046	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
Y/L	0.9231	likely_pathogenic	0.9302	pathogenic	-1.055	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
Y/M	0.9907	likely_pathogenic	0.9927	pathogenic	-1.141	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
Y/N	0.9967	likely_pathogenic	0.9971	pathogenic	-2.985	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.629510437	None	None	N
Y/P	0.9991	likely_pathogenic	0.9994	pathogenic	-1.564	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/Q	0.9996	likely_pathogenic	0.9997	pathogenic	-2.6	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/R	0.998	likely_pathogenic	0.9984	pathogenic	-2.177	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
Y/S	0.9962	likely_pathogenic	0.9966	pathogenic	-3.257	Highly Destabilizing	1.0	D	0.882	deleterious	D	0.629510437	None	None	N
Y/T	0.9983	likely_pathogenic	0.9986	pathogenic	-2.879	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/V	0.9387	likely_pathogenic	0.9462	pathogenic	-1.564	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
Y/W	0.7949	likely_pathogenic	0.8163	pathogenic	-0.268	Destabilizing	1.0	D	0.783	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.