TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5606	17041;17042;17043	chr2:178732153;178732152;178732151	chr2:179596880;179596879;179596878
N2AB	5289	16090;16091;16092	chr2:178732153;178732152;178732151	chr2:179596880;179596879;179596878
N2A	4362	13309;13310;13311	chr2:178732153;178732152;178732151	chr2:179596880;179596879;179596878
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-39
• Domain position: 64
• Structural Position: 144
• Q(SASA): 0.1158
• 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
V/A	rs1356962832	-1.875	0.027	N	0.427	0.23	0.393316636838	gnomAD-4.0.0	2.73687E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59795E-06	0	0
V/F	None	None	0.317	D	0.624	0.212	0.557519804684	gnomAD-4.0.0	1.59131E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85843E-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
V/A	0.1049	likely_benign	0.1026	benign	-1.63	Destabilizing	0.027	N	0.427	neutral	N	0.443440404	None	None	N
V/C	0.6308	likely_pathogenic	0.6357	pathogenic	-2.261	Highly Destabilizing	0.001	N	0.346	neutral	None	None	None	None	N
V/D	0.6047	likely_pathogenic	0.6322	pathogenic	-3.073	Highly Destabilizing	0.317	N	0.637	neutral	N	0.509430395	None	None	N
V/E	0.6159	likely_pathogenic	0.6166	pathogenic	-3.008	Highly Destabilizing	0.38	N	0.622	neutral	None	None	None	None	N
V/F	0.2364	likely_benign	0.2139	benign	-1.344	Destabilizing	0.317	N	0.624	neutral	D	0.542474035	None	None	N
V/G	0.2441	likely_benign	0.2478	benign	-1.96	Destabilizing	0.117	N	0.612	neutral	D	0.535674952	None	None	N
V/H	0.7443	likely_pathogenic	0.7431	pathogenic	-1.42	Destabilizing	0.935	D	0.594	neutral	None	None	None	None	N
V/I	0.0715	likely_benign	0.0675	benign	-0.778	Destabilizing	None	N	0.183	neutral	N	0.482825512	None	None	N
V/K	0.6954	likely_pathogenic	0.6925	pathogenic	-1.604	Destabilizing	0.38	N	0.619	neutral	None	None	None	None	N
V/L	0.1738	likely_benign	0.1556	benign	-0.778	Destabilizing	0.009	N	0.401	neutral	N	0.441885753	None	None	N
V/M	0.1502	likely_benign	0.1394	benign	-1.061	Destabilizing	0.38	N	0.557	neutral	None	None	None	None	N
V/N	0.393	ambiguous	0.3884	ambiguous	-1.89	Destabilizing	0.38	N	0.641	neutral	None	None	None	None	N
V/P	0.5287	ambiguous	0.5377	ambiguous	-1.034	Destabilizing	0.555	D	0.621	neutral	None	None	None	None	N
V/Q	0.6166	likely_pathogenic	0.6145	pathogenic	-2.057	Highly Destabilizing	0.555	D	0.617	neutral	None	None	None	None	N
V/R	0.573	likely_pathogenic	0.5652	pathogenic	-1.124	Destabilizing	0.555	D	0.657	neutral	None	None	None	None	N
V/S	0.2092	likely_benign	0.2032	benign	-2.313	Highly Destabilizing	0.007	N	0.437	neutral	None	None	None	None	N
V/T	0.1257	likely_benign	0.1236	benign	-2.137	Highly Destabilizing	0.081	N	0.502	neutral	None	None	None	None	N
V/W	0.8422	likely_pathogenic	0.8427	pathogenic	-1.63	Destabilizing	0.935	D	0.604	neutral	None	None	None	None	N
V/Y	0.6648	likely_pathogenic	0.6524	pathogenic	-1.275	Destabilizing	0.555	D	0.642	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.