TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25871	77836;77837;77838	chr2:178568521;178568520;178568519	chr2:179433248;179433247;179433246
N2AB	24230	72913;72914;72915	chr2:178568521;178568520;178568519	chr2:179433248;179433247;179433246
N2A	23303	70132;70133;70134	chr2:178568521;178568520;178568519	chr2:179433248;179433247;179433246
N2B	16806	50641;50642;50643	chr2:178568521;178568520;178568519	chr2:179433248;179433247;179433246
Novex-1	16931	51016;51017;51018	chr2:178568521;178568520;178568519	chr2:179433248;179433247;179433246
Novex-2	16998	51217;51218;51219	chr2:178568521;178568520;178568519	chr2:179433248;179433247;179433246
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-136
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.2572
• 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	None	None	0.001	N	0.451	0.146	0.193865811164	gnomAD-4.0.0	1.592E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88296E-05	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
T/A	0.0784	likely_benign	0.0804	benign	-0.946	Destabilizing	None	N	0.288	neutral	N	0.497417937	None	None	N
T/C	0.2741	likely_benign	0.2716	benign	-0.862	Destabilizing	0.883	D	0.621	neutral	None	None	None	None	N
T/D	0.4163	ambiguous	0.3987	ambiguous	-1.245	Destabilizing	0.124	N	0.621	neutral	None	None	None	None	N
T/E	0.2905	likely_benign	0.2658	benign	-1.181	Destabilizing	0.22	N	0.619	neutral	None	None	None	None	N
T/F	0.2223	likely_benign	0.1984	benign	-0.943	Destabilizing	0.497	N	0.657	neutral	None	None	None	None	N
T/G	0.2965	likely_benign	0.2667	benign	-1.249	Destabilizing	0.055	N	0.588	neutral	None	None	None	None	N
T/H	0.1883	likely_benign	0.1832	benign	-1.542	Destabilizing	0.667	D	0.643	neutral	None	None	None	None	N
T/I	0.1094	likely_benign	0.095	benign	-0.207	Destabilizing	0.001	N	0.451	neutral	N	0.510529401	None	None	N
T/K	0.1754	likely_benign	0.1548	benign	-0.824	Destabilizing	0.175	N	0.621	neutral	N	0.49732803	None	None	N
T/L	0.0867	likely_benign	0.0767	benign	-0.207	Destabilizing	0.02	N	0.541	neutral	None	None	None	None	N
T/M	0.0809	likely_benign	0.0724	benign	0.046	Stabilizing	0.497	N	0.63	neutral	None	None	None	None	N
T/N	0.136	likely_benign	0.1299	benign	-1.096	Destabilizing	0.002	N	0.288	neutral	None	None	None	None	N
T/P	0.7626	likely_pathogenic	0.7547	pathogenic	-0.421	Destabilizing	0.427	N	0.625	neutral	D	0.536793225	None	None	N
T/Q	0.181	likely_benign	0.1711	benign	-1.234	Destabilizing	0.667	D	0.634	neutral	None	None	None	None	N
T/R	0.1436	likely_benign	0.1309	benign	-0.651	Destabilizing	0.427	N	0.623	neutral	D	0.524842706	None	None	N
T/S	0.108	likely_benign	0.104	benign	-1.283	Destabilizing	0.003	N	0.309	neutral	N	0.499947048	None	None	N
T/V	0.0863	likely_benign	0.0767	benign	-0.421	Destabilizing	0.004	N	0.306	neutral	None	None	None	None	N
T/W	0.5469	ambiguous	0.4991	ambiguous	-0.944	Destabilizing	0.958	D	0.66	neutral	None	None	None	None	N
T/Y	0.2519	likely_benign	0.2384	benign	-0.639	Destabilizing	0.667	D	0.651	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.