TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7168	21727;21728;21729	chr2:178723598;178723597;178723596	chr2:179588325;179588324;179588323
N2AB	6851	20776;20777;20778	chr2:178723598;178723597;178723596	chr2:179588325;179588324;179588323
N2A	5924	17995;17996;17997	chr2:178723598;178723597;178723596	chr2:179588325;179588324;179588323
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: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-56
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2813
• 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	None	None	0.91	D	0.683	0.572	0.74991972993	gnomAD-4.0.0	1.3689E-06	None	None	None	None	N	None	2.98989E-05	0	None	0	0	None	0	0	0	0	1.65788E-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
V/A	0.4049	ambiguous	0.4252	ambiguous	-1.625	Destabilizing	0.91	D	0.683	prob.neutral	D	0.587086821	None	None	N
V/C	0.8764	likely_pathogenic	0.8902	pathogenic	-1.028	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
V/D	0.8795	likely_pathogenic	0.8972	pathogenic	-1.553	Destabilizing	0.994	D	0.85	deleterious	D	0.629653315	None	None	N
V/E	0.7725	likely_pathogenic	0.7944	pathogenic	-1.457	Destabilizing	0.996	D	0.843	deleterious	None	None	None	None	N
V/F	0.3575	ambiguous	0.3853	ambiguous	-1.056	Destabilizing	0.989	D	0.761	deleterious	D	0.552060319	None	None	N
V/G	0.4346	ambiguous	0.4672	ambiguous	-2.044	Highly Destabilizing	0.994	D	0.813	deleterious	D	0.629653315	None	None	N
V/H	0.9237	likely_pathogenic	0.9347	pathogenic	-1.63	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
V/I	0.097	likely_benign	0.0996	benign	-0.53	Destabilizing	0.248	N	0.309	neutral	N	0.477193193	None	None	N
V/K	0.8286	likely_pathogenic	0.8459	pathogenic	-1.348	Destabilizing	0.996	D	0.843	deleterious	None	None	None	None	N
V/L	0.3431	ambiguous	0.3578	ambiguous	-0.53	Destabilizing	0.071	N	0.326	neutral	D	0.562000144	None	None	N
V/M	0.2543	likely_benign	0.2732	benign	-0.424	Destabilizing	0.991	D	0.664	neutral	None	None	None	None	N
V/N	0.7877	likely_pathogenic	0.8123	pathogenic	-1.277	Destabilizing	0.996	D	0.851	deleterious	None	None	None	None	N
V/P	0.8793	likely_pathogenic	0.8884	pathogenic	-0.862	Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
V/Q	0.8088	likely_pathogenic	0.8325	pathogenic	-1.296	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
V/R	0.7909	likely_pathogenic	0.8156	pathogenic	-1.002	Destabilizing	0.996	D	0.847	deleterious	None	None	None	None	N
V/S	0.6472	likely_pathogenic	0.685	pathogenic	-1.858	Destabilizing	0.983	D	0.833	deleterious	None	None	None	None	N
V/T	0.4951	ambiguous	0.5141	ambiguous	-1.63	Destabilizing	0.304	N	0.41	neutral	None	None	None	None	N
V/W	0.9139	likely_pathogenic	0.9275	pathogenic	-1.373	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/Y	0.7791	likely_pathogenic	0.7995	pathogenic	-1.029	Destabilizing	0.999	D	0.737	prob.delet.	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.