TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31639	95140;95141;95142	chr2:178546416;178546415;178546414	chr2:179411143;179411142;179411141
N2AB	29998	90217;90218;90219	chr2:178546416;178546415;178546414	chr2:179411143;179411142;179411141
N2A	29071	87436;87437;87438	chr2:178546416;178546415;178546414	chr2:179411143;179411142;179411141
N2B	22574	67945;67946;67947	chr2:178546416;178546415;178546414	chr2:179411143;179411142;179411141
Novex-1	22699	68320;68321;68322	chr2:178546416;178546415;178546414	chr2:179411143;179411142;179411141
Novex-2	22766	68521;68522;68523	chr2:178546416;178546415;178546414	chr2:179411143;179411142;179411141
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-152
• Domain position: 19
• Structural Position: 35
• Q(SASA): 0.247
• 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	rs759136839	-1.733	0.939	N	0.59	0.581	0.57068417637	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
V/A	rs759136839	-1.733	0.939	N	0.59	0.581	0.57068417637	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	0	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	0.4728	ambiguous	0.477	ambiguous	-0.93	Destabilizing	0.939	D	0.59	neutral	N	0.51024976	None	None	N
V/C	0.9412	likely_pathogenic	0.9394	pathogenic	-0.946	Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	N
V/D	0.9953	likely_pathogenic	0.9954	pathogenic	-0.199	Destabilizing	0.997	D	0.837	deleterious	D	0.601552468	None	None	N
V/E	0.9841	likely_pathogenic	0.9845	pathogenic	-0.229	Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	N
V/F	0.6016	likely_pathogenic	0.6005	pathogenic	-0.749	Destabilizing	0.982	D	0.797	deleterious	D	0.540079779	None	None	N
V/G	0.8706	likely_pathogenic	0.8762	pathogenic	-1.186	Destabilizing	0.997	D	0.827	deleterious	D	0.585533107	None	None	N
V/H	0.9929	likely_pathogenic	0.9926	pathogenic	-0.621	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
V/I	0.093	likely_benign	0.0931	benign	-0.358	Destabilizing	0.046	N	0.224	neutral	N	0.465264045	None	None	N
V/K	0.987	likely_pathogenic	0.9861	pathogenic	-0.74	Destabilizing	0.993	D	0.819	deleterious	None	None	None	None	N
V/L	0.5464	ambiguous	0.5358	ambiguous	-0.358	Destabilizing	0.76	D	0.59	neutral	D	0.558178757	None	None	N
V/M	0.5484	ambiguous	0.5474	ambiguous	-0.472	Destabilizing	0.986	D	0.757	deleterious	None	None	None	None	N
V/N	0.9857	likely_pathogenic	0.9854	pathogenic	-0.553	Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
V/P	0.9764	likely_pathogenic	0.9753	pathogenic	-0.512	Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
V/Q	0.9801	likely_pathogenic	0.9789	pathogenic	-0.673	Destabilizing	0.998	D	0.835	deleterious	None	None	None	None	N
V/R	0.9729	likely_pathogenic	0.9709	pathogenic	-0.31	Destabilizing	0.998	D	0.856	deleterious	None	None	None	None	N
V/S	0.859	likely_pathogenic	0.8606	pathogenic	-1.114	Destabilizing	0.993	D	0.807	deleterious	None	None	None	None	N
V/T	0.5291	ambiguous	0.5237	ambiguous	-1.015	Destabilizing	0.953	D	0.679	prob.neutral	None	None	None	None	N
V/W	0.989	likely_pathogenic	0.9885	pathogenic	-0.85	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
V/Y	0.9601	likely_pathogenic	0.9577	pathogenic	-0.557	Destabilizing	0.998	D	0.794	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.