TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29699	89320;89321;89322	chr2:178554016;178554015;178554014	chr2:179418743;179418742;179418741
N2AB	28058	84397;84398;84399	chr2:178554016;178554015;178554014	chr2:179418743;179418742;179418741
N2A	27131	81616;81617;81618	chr2:178554016;178554015;178554014	chr2:179418743;179418742;179418741
N2B	20634	62125;62126;62127	chr2:178554016;178554015;178554014	chr2:179418743;179418742;179418741
Novex-1	20759	62500;62501;62502	chr2:178554016;178554015;178554014	chr2:179418743;179418742;179418741
Novex-2	20826	62701;62702;62703	chr2:178554016;178554015;178554014	chr2:179418743;179418742;179418741
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: Fn3-104
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.3968
• 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/A	None	None	0.201	N	0.351	0.103	0.12205267543	gnomAD-4.0.0	6.84309E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9947E-07	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	0.0727	likely_benign	0.085	benign	-0.721	Destabilizing	0.201	N	0.351	neutral	N	0.495431371	None	None	N
T/C	0.2955	likely_benign	0.3772	ambiguous	-0.368	Destabilizing	0.992	D	0.397	neutral	None	None	None	None	N
T/D	0.4544	ambiguous	0.6066	pathogenic	0.257	Stabilizing	0.85	D	0.415	neutral	None	None	None	None	N
T/E	0.3231	likely_benign	0.4208	ambiguous	0.219	Stabilizing	0.617	D	0.416	neutral	None	None	None	None	N
T/F	0.1775	likely_benign	0.2442	benign	-1.021	Destabilizing	0.85	D	0.429	neutral	None	None	None	None	N
T/G	0.203	likely_benign	0.2741	benign	-0.915	Destabilizing	0.617	D	0.405	neutral	None	None	None	None	N
T/H	0.2187	likely_benign	0.285	benign	-1.129	Destabilizing	0.992	D	0.416	neutral	None	None	None	None	N
T/I	0.0883	likely_benign	0.1147	benign	-0.312	Destabilizing	0.004	N	0.218	neutral	N	0.420704326	None	None	N
T/K	0.2104	likely_benign	0.2616	benign	-0.472	Destabilizing	0.549	D	0.412	neutral	N	0.467396621	None	None	N
T/L	0.0631	likely_benign	0.0762	benign	-0.312	Destabilizing	0.103	N	0.417	neutral	None	None	None	None	N
T/M	0.0673	likely_benign	0.0749	benign	-0.065	Destabilizing	0.103	N	0.403	neutral	None	None	None	None	N
T/N	0.1103	likely_benign	0.1472	benign	-0.303	Destabilizing	0.85	D	0.39	neutral	None	None	None	None	N
T/P	0.1598	likely_benign	0.2407	benign	-0.417	Destabilizing	0.963	D	0.422	neutral	D	0.524484841	None	None	N
T/Q	0.1898	likely_benign	0.2283	benign	-0.492	Destabilizing	0.92	D	0.419	neutral	None	None	None	None	N
T/R	0.1809	likely_benign	0.2309	benign	-0.204	Destabilizing	0.81	D	0.41	neutral	N	0.455179472	None	None	N
T/S	0.0986	likely_benign	0.1218	benign	-0.617	Destabilizing	0.045	N	0.227	neutral	N	0.459067926	None	None	N
T/V	0.0792	likely_benign	0.0924	benign	-0.417	Destabilizing	0.009	N	0.093	neutral	None	None	None	None	N
T/W	0.4648	ambiguous	0.5737	pathogenic	-0.95	Destabilizing	0.992	D	0.474	neutral	None	None	None	None	N
T/Y	0.2408	likely_benign	0.3072	benign	-0.705	Destabilizing	0.92	D	0.428	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.