TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9698	29317;29318;29319	chr2:178706904;178706903;178706902	chr2:179571631;179571630;179571629
N2AB	9381	28366;28367;28368	chr2:178706904;178706903;178706902	chr2:179571631;179571630;179571629
N2A	8454	25585;25586;25587	chr2:178706904;178706903;178706902	chr2:179571631;179571630;179571629
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: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-83
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.146
• 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
L/V	None	None	0.939	None	0.546	0.173	0.573031010871	gnomAD-4.0.0	3.18886E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72528E-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
L/A	0.9267	likely_pathogenic	0.9265	pathogenic	-1.729	Destabilizing	0.91	D	0.529	neutral	None	None	None	None	N
L/C	0.9489	likely_pathogenic	0.9363	pathogenic	-0.918	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
L/D	0.9954	likely_pathogenic	0.9966	pathogenic	-0.913	Destabilizing	0.986	D	0.723	prob.delet.	None	None	None	None	N
L/E	0.9834	likely_pathogenic	0.9882	pathogenic	-0.845	Destabilizing	0.986	D	0.72	prob.delet.	None	None	None	None	N
L/F	0.8184	likely_pathogenic	0.8293	pathogenic	-1.036	Destabilizing	0.1	N	0.306	neutral	None	None	None	None	N
L/G	0.9806	likely_pathogenic	0.9813	pathogenic	-2.117	Highly Destabilizing	0.973	D	0.689	prob.neutral	None	None	None	None	N
L/H	0.9639	likely_pathogenic	0.9682	pathogenic	-1.326	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
L/I	0.3152	likely_benign	0.3177	benign	-0.703	Destabilizing	0.939	D	0.539	neutral	None	None	None	None	N
L/K	0.9532	likely_pathogenic	0.969	pathogenic	-0.986	Destabilizing	0.986	D	0.679	prob.neutral	None	None	None	None	N
L/M	0.5657	likely_pathogenic	0.5563	ambiguous	-0.573	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	N
L/N	0.9677	likely_pathogenic	0.9747	pathogenic	-0.873	Destabilizing	0.986	D	0.724	prob.delet.	None	None	None	None	N
L/P	0.7352	likely_pathogenic	0.7138	pathogenic	-1.015	Destabilizing	0.991	D	0.729	prob.delet.	None	None	None	None	N
L/Q	0.9467	likely_pathogenic	0.9594	pathogenic	-0.957	Destabilizing	0.993	D	0.691	prob.neutral	None	None	None	None	N
L/R	0.9198	likely_pathogenic	0.9381	pathogenic	-0.544	Destabilizing	0.982	D	0.684	prob.neutral	None	None	None	None	N
L/S	0.98	likely_pathogenic	0.9809	pathogenic	-1.601	Destabilizing	0.386	N	0.369	neutral	None	None	None	None	N
L/T	0.9254	likely_pathogenic	0.9345	pathogenic	-1.41	Destabilizing	0.91	D	0.635	neutral	None	None	None	None	N
L/V	0.376	ambiguous	0.3788	ambiguous	-1.015	Destabilizing	0.939	D	0.546	neutral	None	None	None	None	N
L/W	0.9557	likely_pathogenic	0.9553	pathogenic	-1.167	Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
L/Y	0.9592	likely_pathogenic	0.9646	pathogenic	-0.907	Destabilizing	0.973	D	0.701	prob.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.