TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25855	77788;77789;77790	chr2:178568569;178568568;178568567	chr2:179433296;179433295;179433294
N2AB	24214	72865;72866;72867	chr2:178568569;178568568;178568567	chr2:179433296;179433295;179433294
N2A	23287	70084;70085;70086	chr2:178568569;178568568;178568567	chr2:179433296;179433295;179433294
N2B	16790	50593;50594;50595	chr2:178568569;178568568;178568567	chr2:179433296;179433295;179433294
Novex-1	16915	50968;50969;50970	chr2:178568569;178568568;178568567	chr2:179433296;179433295;179433294
Novex-2	16982	51169;51170;51171	chr2:178568569;178568568;178568567	chr2:179433296;179433295;179433294
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-136
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0892
• 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/F	rs1409816119	-1.727	1.0	N	0.815	0.646	0.674917227544	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
L/F	rs1409816119	-1.727	1.0	N	0.815	0.646	0.674917227544	gnomAD-4.0.0	1.59192E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.0259E-05

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	0.9269	likely_pathogenic	0.9384	pathogenic	-2.494	Highly Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
L/C	0.8856	likely_pathogenic	0.9036	pathogenic	-2.128	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9997	pathogenic	-3.177	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
L/E	0.9977	likely_pathogenic	0.9982	pathogenic	-2.84	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/F	0.3696	ambiguous	0.4077	ambiguous	-1.554	Destabilizing	1.0	D	0.815	deleterious	N	0.512481815	None	None	N
L/G	0.991	likely_pathogenic	0.9931	pathogenic	-3.127	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
L/H	0.9896	likely_pathogenic	0.9926	pathogenic	-3.04	Highly Destabilizing	1.0	D	0.856	deleterious	D	0.56339122	None	None	N
L/I	0.1288	likely_benign	0.1392	benign	-0.589	Destabilizing	0.999	D	0.657	neutral	D	0.53654814	None	None	N
L/K	0.9951	likely_pathogenic	0.9963	pathogenic	-1.965	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/M	0.2618	likely_benign	0.2829	benign	-0.951	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
L/N	0.9977	likely_pathogenic	0.9984	pathogenic	-2.706	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
L/P	0.997	likely_pathogenic	0.9981	pathogenic	-1.214	Destabilizing	1.0	D	0.891	deleterious	D	0.574747525	None	None	N
L/Q	0.9887	likely_pathogenic	0.9916	pathogenic	-2.285	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/R	0.9879	likely_pathogenic	0.9908	pathogenic	-2.201	Highly Destabilizing	1.0	D	0.884	deleterious	D	0.574747525	None	None	N
L/S	0.9933	likely_pathogenic	0.9954	pathogenic	-3.292	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/T	0.9749	likely_pathogenic	0.9809	pathogenic	-2.768	Highly Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
L/V	0.179	likely_benign	0.1848	benign	-1.214	Destabilizing	0.999	D	0.661	neutral	D	0.526395788	None	None	N
L/W	0.9275	likely_pathogenic	0.9442	pathogenic	-1.93	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
L/Y	0.9266	likely_pathogenic	0.9424	pathogenic	-1.7	Destabilizing	1.0	D	0.85	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.