TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22439	67540;67541;67542	chr2:178579972;178579971;178579970	chr2:179444699;179444698;179444697
N2AB	20798	62617;62618;62619	chr2:178579972;178579971;178579970	chr2:179444699;179444698;179444697
N2A	19871	59836;59837;59838	chr2:178579972;178579971;178579970	chr2:179444699;179444698;179444697
N2B	13374	40345;40346;40347	chr2:178579972;178579971;178579970	chr2:179444699;179444698;179444697
Novex-1	13499	40720;40721;40722	chr2:178579972;178579971;178579970	chr2:179444699;179444698;179444697
Novex-2	13566	40921;40922;40923	chr2:178579972;178579971;178579970	chr2:179444699;179444698;179444697
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-50
• Domain position: 86
• Structural Position: 120
• Q(SASA): 0.2791
• Predicted PPI site: I

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
P/A	rs987188592	None	0.9	N	0.531	0.241	0.313818047136	gnomAD-4.0.0	1.59262E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86036E-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
P/A	0.094	likely_benign	0.0819	benign	-1.565	Destabilizing	0.9	D	0.531	neutral	N	0.47378464	None	None	I
P/C	0.6169	likely_pathogenic	0.5722	pathogenic	-0.874	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
P/D	0.8991	likely_pathogenic	0.8945	pathogenic	-1.469	Destabilizing	0.998	D	0.596	neutral	None	None	None	None	I
P/E	0.7225	likely_pathogenic	0.7238	pathogenic	-1.429	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	I
P/F	0.7494	likely_pathogenic	0.7115	pathogenic	-1.101	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
P/G	0.4805	ambiguous	0.4004	ambiguous	-1.917	Destabilizing	0.071	N	0.487	neutral	None	None	None	None	I
P/H	0.6141	likely_pathogenic	0.5873	pathogenic	-1.424	Destabilizing	1.0	D	0.715	prob.delet.	D	0.538203171	None	None	I
P/I	0.6697	likely_pathogenic	0.692	pathogenic	-0.679	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	I
P/K	0.83	likely_pathogenic	0.8457	pathogenic	-1.231	Destabilizing	0.998	D	0.59	neutral	None	None	None	None	I
P/L	0.4724	ambiguous	0.5036	ambiguous	-0.679	Destabilizing	0.997	D	0.722	prob.delet.	D	0.535921765	None	None	I
P/M	0.6567	likely_pathogenic	0.6488	pathogenic	-0.491	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
P/N	0.8269	likely_pathogenic	0.8082	pathogenic	-1.089	Destabilizing	0.998	D	0.661	neutral	None	None	None	None	I
P/Q	0.5767	likely_pathogenic	0.5735	pathogenic	-1.221	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	I
P/R	0.6952	likely_pathogenic	0.7242	pathogenic	-0.727	Destabilizing	0.999	D	0.701	prob.neutral	D	0.522212056	None	None	I
P/S	0.2796	likely_benign	0.2404	benign	-1.626	Destabilizing	0.978	D	0.529	neutral	N	0.509930698	None	None	I
P/T	0.312	likely_benign	0.319	benign	-1.481	Destabilizing	0.997	D	0.593	neutral	N	0.519338447	None	None	I
P/V	0.5004	ambiguous	0.5183	ambiguous	-0.941	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	I
P/W	0.8926	likely_pathogenic	0.8815	pathogenic	-1.363	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
P/Y	0.7702	likely_pathogenic	0.7521	pathogenic	-1.046	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I

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.