TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30188	90787;90788;90789	chr2:178552338;178552337;178552336	chr2:179417065;179417064;179417063
N2AB	28547	85864;85865;85866	chr2:178552338;178552337;178552336	chr2:179417065;179417064;179417063
N2A	27620	83083;83084;83085	chr2:178552338;178552337;178552336	chr2:179417065;179417064;179417063
N2B	21123	63592;63593;63594	chr2:178552338;178552337;178552336	chr2:179417065;179417064;179417063
Novex-1	21248	63967;63968;63969	chr2:178552338;178552337;178552336	chr2:179417065;179417064;179417063
Novex-2	21315	64168;64169;64170	chr2:178552338;178552337;178552336	chr2:179417065;179417064;179417063
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-148
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.226
• 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
T/I	rs1456715081	None	0.004	N	0.365	0.201	0.349647731962	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1456715081	None	0.004	N	0.365	0.201	0.349647731962	gnomAD-4.0.0	2.49705E-06	None	None	None	None	N	None	0	0	None	0	2.23464E-05	None	0	0	1.70194E-06	1.13327E-05	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
T/A	0.0905	likely_benign	0.0866	benign	-1.023	Destabilizing	0.007	N	0.149	neutral	N	0.515284647	None	None	N
T/C	0.3024	likely_benign	0.2933	benign	-0.852	Destabilizing	0.992	D	0.575	neutral	None	None	None	None	N
T/D	0.6259	likely_pathogenic	0.5898	pathogenic	-1.744	Destabilizing	0.617	D	0.515	neutral	None	None	None	None	N
T/E	0.5351	ambiguous	0.4853	ambiguous	-1.543	Destabilizing	0.617	D	0.494	neutral	None	None	None	None	N
T/F	0.2212	likely_benign	0.2204	benign	-0.639	Destabilizing	0.85	D	0.632	neutral	None	None	None	None	N
T/G	0.2523	likely_benign	0.2366	benign	-1.45	Destabilizing	0.25	N	0.533	neutral	None	None	None	None	N
T/H	0.2696	likely_benign	0.2664	benign	-1.676	Destabilizing	0.992	D	0.624	neutral	None	None	None	None	N
T/I	0.1559	likely_benign	0.1408	benign	0.095	Stabilizing	0.004	N	0.365	neutral	N	0.512823132	None	None	N
T/K	0.3482	ambiguous	0.2978	benign	-0.683	Destabilizing	0.617	D	0.495	neutral	None	None	None	None	N
T/L	0.1113	likely_benign	0.1066	benign	0.095	Stabilizing	0.103	N	0.489	neutral	None	None	None	None	N
T/M	0.0991	likely_benign	0.0951	benign	0.087	Stabilizing	0.85	D	0.582	neutral	None	None	None	None	N
T/N	0.1627	likely_benign	0.151	benign	-1.435	Destabilizing	0.549	D	0.533	neutral	N	0.495081441	None	None	N
T/P	0.7201	likely_pathogenic	0.7308	pathogenic	-0.245	Destabilizing	0.896	D	0.557	neutral	D	0.53007541	None	None	N
T/Q	0.2954	likely_benign	0.2807	benign	-1.173	Destabilizing	0.92	D	0.575	neutral	None	None	None	None	N
T/R	0.2851	likely_benign	0.2534	benign	-0.932	Destabilizing	0.85	D	0.567	neutral	None	None	None	None	N
T/S	0.1054	likely_benign	0.1021	benign	-1.572	Destabilizing	0.007	N	0.169	neutral	N	0.493714509	None	None	N
T/V	0.134	likely_benign	0.1232	benign	-0.245	Destabilizing	0.103	N	0.496	neutral	None	None	None	None	N
T/W	0.613	likely_pathogenic	0.611	pathogenic	-0.881	Destabilizing	0.992	D	0.651	neutral	None	None	None	None	N
T/Y	0.2594	likely_benign	0.26	benign	-0.481	Destabilizing	0.92	D	0.643	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.