TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18213	54862;54863;54864	chr2:178604050;178604049;178604048	chr2:179468777;179468776;179468775
N2AB	16572	49939;49940;49941	chr2:178604050;178604049;178604048	chr2:179468777;179468776;179468775
N2A	15645	47158;47159;47160	chr2:178604050;178604049;178604048	chr2:179468777;179468776;179468775
N2B	9148	27667;27668;27669	chr2:178604050;178604049;178604048	chr2:179468777;179468776;179468775
Novex-1	9273	28042;28043;28044	chr2:178604050;178604049;178604048	chr2:179468777;179468776;179468775
Novex-2	9340	28243;28244;28245	chr2:178604050;178604049;178604048	chr2:179468777;179468776;179468775
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Fn3-20
• Domain position: 48
• Structural Position: 65
• Q(SASA): 0.2468
• 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
W/S	None	None	0.942	N	0.681	0.474	0.795843823839	gnomAD-4.0.0	1.59315E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86256E-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
W/A	0.9957	likely_pathogenic	0.9894	pathogenic	-2.874	Highly Destabilizing	0.754	D	0.591	neutral	None	None	None	None	N
W/C	0.9971	likely_pathogenic	0.9923	pathogenic	-1.215	Destabilizing	0.032	N	0.34	neutral	D	0.524832176	None	None	N
W/D	0.9977	likely_pathogenic	0.9967	pathogenic	-1.613	Destabilizing	0.993	D	0.677	prob.neutral	None	None	None	None	N
W/E	0.9984	likely_pathogenic	0.9975	pathogenic	-1.526	Destabilizing	0.993	D	0.672	neutral	None	None	None	None	N
W/F	0.6405	likely_pathogenic	0.5886	pathogenic	-1.715	Destabilizing	0.978	D	0.539	neutral	None	None	None	None	N
W/G	0.9777	likely_pathogenic	0.9521	pathogenic	-3.066	Highly Destabilizing	0.942	D	0.554	neutral	N	0.517488342	None	None	N
W/H	0.9923	likely_pathogenic	0.9869	pathogenic	-1.387	Destabilizing	0.998	D	0.575	neutral	None	None	None	None	N
W/I	0.9932	likely_pathogenic	0.9825	pathogenic	-2.17	Highly Destabilizing	0.956	D	0.676	prob.neutral	None	None	None	None	N
W/K	0.9994	likely_pathogenic	0.9988	pathogenic	-1.407	Destabilizing	0.978	D	0.672	neutral	None	None	None	None	N
W/L	0.9812	likely_pathogenic	0.95	pathogenic	-2.17	Highly Destabilizing	0.698	D	0.529	neutral	N	0.503939536	None	None	N
W/M	0.9968	likely_pathogenic	0.9925	pathogenic	-1.668	Destabilizing	0.998	D	0.583	neutral	None	None	None	None	N
W/N	0.9982	likely_pathogenic	0.9968	pathogenic	-1.745	Destabilizing	0.993	D	0.658	neutral	None	None	None	None	N
W/P	0.9946	likely_pathogenic	0.9923	pathogenic	-2.422	Highly Destabilizing	0.993	D	0.659	neutral	None	None	None	None	N
W/Q	0.9992	likely_pathogenic	0.9981	pathogenic	-1.758	Destabilizing	0.993	D	0.611	neutral	None	None	None	None	N
W/R	0.998	likely_pathogenic	0.996	pathogenic	-0.859	Destabilizing	0.99	D	0.671	neutral	N	0.512461912	None	None	N
W/S	0.9909	likely_pathogenic	0.9789	pathogenic	-2.212	Highly Destabilizing	0.942	D	0.681	prob.neutral	N	0.502738221	None	None	N
W/T	0.9946	likely_pathogenic	0.9877	pathogenic	-2.082	Highly Destabilizing	0.956	D	0.579	neutral	None	None	None	None	N
W/V	0.9911	likely_pathogenic	0.9783	pathogenic	-2.422	Highly Destabilizing	0.915	D	0.67	neutral	None	None	None	None	N
W/Y	0.8689	likely_pathogenic	0.8279	pathogenic	-1.424	Destabilizing	0.993	D	0.534	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.